Canagliflozin (Cana) has protected against diabetes-related cardiovascular disease. This study was intended to explore the effect and molecular mechanism of Cana on cardiovascular protection in type 2 diabetic coronary atherosclerotic heart disease (CAD).

We constructed a rat model of type 2 diabetic CAD and examined its physiological and biochemical indices before and after Cana treatment. Next-generation transcriptome sequencing was performed on rat cardiac tissue. Various functional and molecular experiments involving Cana treatment and the natriuretic peptide B (NPPB) gene were performed on human cardiomyocytes (AC16 cells).

The physiological, biochemical, and imaging parameters of the model rats were abnormal. Cana treatment reversed these injuries. In all, 369 differentially expressed genes were discovered by next-generation transcriptome sequencing; NPPB was identified as the target gene. Cana treatment significantly improved the function of AC16 cells treated with high glucose and significantly upregulated the expression level of the NPPB gene. The NPPB gene significantly increased the viability of AC16 cells and significantly decreased the apoptosis rate and reactive oxygen species (ROS) level. In addition, NPPB significantly upregulated the expression of B-cell lymphoma 2 (Bcl-2) and downregulated the expression of Bcl-2 associated X protein (Bax). Cana treatment further improved these cellular functions and protein expression levels. Furthermore, the NPPB gene significantly upregulated protein kinase 1-α (PKG1α) expression level and Cana treatment enhanced the regulatory effect of NPPB on PKG1α.

The cardiovascular protective effect of Cana in diabetes mellitus was mediated by upregulating the expression of NPPB and upregulating the level of PKG1α, which in turn regulated the viability, apoptosis rate, and ROS level of AC16 cells.

Objectives: This study engineered a colon-targeted drug delivery system (CTDS) using the dual pharmaceutical and edible properties of Pueraria lobata to encapsulate Lactobacillus paracasei for Type 2 diabetes mellitus (T2DM) therapy. Methods: The CTDS was designed as a core-shell composite through microwave-hydrothermal engineering, comprising the following: (1) a retrograded starch shell with acid/enzyme-resistant crystallinity to protect probiotics from gastric degradation; (2) a porous cellulose core derived from Pueraria lobata's natural microstructure, serving as a colonization scaffold for probiotics. Results: Structural characterization confirmed the shell's resistance to acidic/pancreatic conditions and the core's hierarchical porosity for bacterial encapsulation. pH/enzyme-responsive release kinetics were validated via fluorescence imaging, demonstrating targeted probiotic delivery to the colon with minimal gastric leakage. In diabetic models, the CTDS significantly reduced fasting blood glucose and improved dyslipidemia, while histopathological analysis revealed restored hepatic and pancreatic tissue architecture. Pharmacologically, the system acted as both a probiotic delivery vehicle and a microbiota modulator, selectively enriching Allobaculum and other short-chain fatty acid (SCFA)-producing bacteria to enhance SCFA biosynthesis and metabolic homeostasis. The CTDS further exhibited direct compression compatibility, enabling its translation into scalable oral dosage forms (e.g., tablets). Conclusions: By integrating natural material engineering, microbiota-targeted delivery, and tissue repair, this platform bridges the gap between pharmaceutical-grade probiotic protection and metabolic intervention in T2DM.

Previous studies have found that miR-4472 is overexpressed in the serum of individuals with obesity and type 2 diabetes mellitus (T2DM), which may participate in the process of obesity-induced T2DM. However, a role for miR-4472 in the process has not been demonstrated. Here, we aim to investigate whether the increased content of miR-4472 in adipose tissue derived from exosomes inhibits glucose uptake in skeletal muscle by downregulating the expression of its target gene.

In vitro C2C12 and 3T3-L1 cells, and in vivo diet-induced obesity mouse models and AT-Dicer KO mice were used to assess the impact of miR-4472 on glucose uptake and insulin sensitivity. We also evaluated the effects of serum exosomes from normal and obese individuals on insulin sensitivity in mice and the expression of miR-4472 and target genes in skeletal muscle.

miR-4472 exhibits a strong positive correlation with BMI, waist circumference, hip circumference, and FPG. The content of miR-4472 derived from adipose tissue exosomes increases in the circulation in a state of obesity, which can induce insulin resistance by targeting the expression of MEF2D/GLUT4, inhibiting the glucose consumption and uptake ability of skeletal muscle cells. Both exosome inhibitors and miR-4472 inhibitors can reverse the inhibitory effect of miR-4472 on MEF2D/GLUT4 expression and glucose intake and uptake ability. Additionally, they can improve insulin resistance caused by increased miR-4472 levels in mice with obesity.

Adipocyte exosome miR-4472 inhibits glucose uptake in skeletal muscle through downregulating the expression of MEF2D/GLUT4.

Increasing evidence has shown a close relation between the pathogenesis of type 2 diabetes mellitus (T2DM), which is a global health problem with multifactorial etiopathogenesis, and gut microbiota.

During in-vitro fermentation of Scrophularia ningpoensis (known as Xuanshen) polysaccharide (SNP) by T2DM gut microbiota, effects of SNP on the gas content, production of short-chain fatty acids (SCFAs), metabolite profile and microbiota composition were studied.

Analysis of chemical compositions indicates that the total sugar content of SNP was found to be as high as 87.35 ± 0.13% (w/w). SNP treatment significantly improved the gas volume and composition in T2DM fecal matter. Moreover, intestinal flora degraded SNP to produce SCFAs, thus regulating SCFA production and composition. Metabolomic analysis implied that SNP shows potential to regulate the five gut metabolites (L-valine, L-leucine, L-isoleucine, L-alanine, and xylitol) in T2DM fecal matter. Furthermore, dysbiosis of gut microbiota induced by T2DM was reversed by SNP. The evidence includes decreasing Firmicutes/Bacteroidota ratio at phylum level promoting proliferation of the bacterial abundance of Dorea, Parabacteroides, Faecalibacterium, and Lachnospira and decreased bacterial abundance of Escherichia-Shigella. Based on these findings, the action mechanism of SNP against T2DM was clarified by reshaping microbiota and regulating intestinal metabolites, and a novel target was provided for interventions of T2DM.

Helicobacter pylori (H. pylori) infection has the capacity to alter the gut microbiota composition. There is a significant correlation between H. pylori infection and type 2 diabetes mellitus (T2DM). Further research is necessary to explore whether gut microbiota plays a role in the relationship between H. pylori and T2DM.

Fecal samples were obtained from 44 patients with T2DM, including 20 who tested positive for H. pylori and 24 who tested negative. Intestinal microbiota composition was analyzed via 16S rRNA V3-V4 amplicon sequencing. Differences in microbial distribution and significant microbial biomarkers were identified between H. pylori positive and negative groups. A Spearman correlation analysis assessed the relationship between intestinal microbiota and glycemic parameters. Additionally, PICRUSt2 was used to predict intestinal bacterial functions.

Results indicate that in H. pylori (+) T2DM patients, HbA1c levels were significantly higher (8.9% vs. 8.1%, p = 0.021), while both the C-peptide peak (3.70 vs. 5.98 ng/mL, p = 0.040) and fasting C-peptide levels (1.42 vs. 2.31 ng/mL, p = 0.008) were significantly lower compared to H. pylori (-) T2DM groups. A total of 11 colonic phyla and 100 genera were identified in all fecal samples. In groups positive for H. pylori, there was a significant enrichment of the phylum Proteobacteria, while the genera Lactobacillus, Butyricimonas, and Akkermansia were significantly reduced (all p < 0.05). Correlation analysis showed that the abundance of the genera Butyricimonas (p = 0.01) and Akkermansia (p = 0.048) were negatively correlated with fasting plasma glucose. KEGG pathway analysis indicated a significant enrichment of methylmalonyl-CoA mutase and succinyl-CoA in H. pylori-infected T2DM patients.

This study suggests that T2DM patients with H. pylori infection exhibit more impaired pancreatic islet function potentially due to H. pylori-induced alterations in the gut microbiota.

Cinnamomi Ramulus (CR) is the dried bark of Cinnamomum cassia Presl, Lauraceae. Puerariae Lobatae Radix (PLR) is the dried root of the Pueraria lobata (Wild.) Ohwi, Leguminosae. This Chinese herb couple come from the classic formula "Gui Zhi Ge Gen Tang," which is included in the TCM classic "Treatise on Febrile Diseases." Our previous studies have found that CR related herbal compound and PLR related herbal compound are useful in improving type 2 diabetes mellitus (T2DM), which is expected to be an antidiabetic candidate with fewer side effects. However the mechanism of action of CR-PLR on T2DM has not yet been fully elucidated.

The decoction of CR-PLR was prepared by aqueous extraction method and the composition of it was analyzed using UPLC-Q-TOF-MS and HPLC. The T2DM model was established by intraperitoneal injection of streptozotocin, and the groups of drug administration were metformin, CR, PLR and CR-PLR groups, with continuous gastric gavage for 6 weeks, and the serological indexes were detected by ELISA. The abundance of rats' gut flora was detected by 16s rDNA sequencing, and changes in the content of short-chain fatty acids (SCFAs) in feces of rats were detected by GC-MS; and the expression of G protein-coupled receptor43 (GPR43) and glucagon-like peptide-1 (GLP-1) proteins in colonic tissues of rats were detected by Western Blot. The pharmacokinetic behavior of CR-PLR was investigated in both normal and T2DM model rats. Caco-2/HT29 co-culture cell model was established in vitro, transepithelial electrical resistance (TEER) and ALP activity of epithelial cells were measured to evaluate cell model integrity and cell polarization, Alcian blue staining was used to verify the presence of mucus production, and CCK-8 was used to screen drug safe concentration. The bidirectional transport of puerarin was studied to investigate the transport mechanism of puerarin and the effect of leuric acid on puerarin transport.

The results indicated that CR-PLR can stimulate intestinal flora, increase the content of SCFAs, activate intestinal GPR43 protein, and promote the secretion of GLP-1 in intestinal L cells, which plays a therapeutic role in the treatment of T2DM. Additionally, cytology and pharmacokinetics experiments have proved that cinnamic acid (CA) can enhance the absorption and transport of puerarin (PUR) by inhibiting the efflux effects mediated by P-gp and MRP efflux transporters. The present study exhibites the scientific and reasonable menaning of this novel Chinese herb couple treating T2DM from the perspecives of pharmacodynamics and pharmacokinetics.

Progranulin (PGRN) is a secreted glycoprotein with cytokine-like properties, exerting tripartite mechanisms of inflammation suppression, tissue repair promotion, and metabolic regulation. This multifaceted functionality positions PGRN as a potential "multi-effect therapeutic strategy" for metabolic disorders characterised by cartilage degradation and imbalanced bone remodelling, potentially establishing it as a novel therapeutic target for such conditions. Osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, osteoporosis, periodontitis, and diabetes-related complications-representing the most prevalent metabolic diseases-currently lack effective treatments due to incomplete understanding of their precise pathogenic mechanisms. Recent studies have revealed that PGRN expression levels are closely associated with the onset and progression of these metabolic disorders. However, the exact regulatory role of PGRN in these diseases remains elusive, partly owing to its tissue-specific actions and context-dependent dual roles (anti-inflammatory vs. pro-inflammatory). In this review, we summarise the structure and functions of PGRN, explore its involvement in neurological disorders, immune-inflammatory diseases, and metabolic conditions, and specifically focus on its molecular mechanisms in metabolic diseases. Furthermore, we consolidate advances in targeting PGRN and the application of its engineered derivative, Atsttrin, in metabolic bone disorders. We also discuss potential unexplored mechanisms through which PGRN may exert influence within this field or other therapeutic domains. Collectively, this work aims to provide a new framework for elucidating PGRN's role in disease pathogenesis and advancing strategies for the prevention and treatment of metabolic disorders.

Type 2 diabetes mellitus (T2DM) is a rapidly increasing metabolic disorder that poses a significant threat to global public health. Recent evidence suggests that targeting the gut microbiota through dietary and pharmaceutical interventions can effectively manage T2DM. In this study, we developed a novel Chinese herbal formula, CCM, specifically for T2DM, composed of Coptis rhizoma, Cinnamomi cortex, and Mume fructus. To evaluate CCM's efficacy and explore its underlying mechanisms, particularly the role of the gut microbiota, diabetic C57/db/db mice were administered different doses of CCM (low, medium, high) for 4 weeks, with normal C57 mice as healthy controls and metformin as a positive control. Comprehensive clinical indicators of T2DM were measured before and after treatment. High-throughput sequencing was used to assess changes in gut microbiome composition and function. Our results showed that CCM treatment, especially at medium and high doses, resulted in more significant improvements in blood glucose, lipid profiles, and body weight compared to metformin. The CCM-treated group also exhibited more significant changes in the microbial community structure compared to the metformin group, notably enriching three beneficial microbes (>40%): Bacteroidetes spp., Akkermansia spp., and Parabacteroides spp., which correlated with improved diabetic parameters. Further analysis identified that all four microbial metabolic pathways linked to lowering blood glucose were exclusively enriched in the CCM-treated group. Of the 10 pathways related to improved blood lipid levels, five were unique to CCM. These unique pathways enriched by CCM may explain its superior therapeutic effects, indicating its distinct mechanisms in modulating gut microbiota.IMPORTANCEOur study demonstrates that CCM outperforms metformin in managing key clinical indicators in type 2 diabetes mellitus (T2DM) model mice and induces more significant alterations in gut microbiota composition and function. Notably, the uniquely enriched beneficial microbes and microbial metabolic pathways in the CCM samples may explain its enhanced therapeutic effects compared to metformin. Consequently, these findings suggest that CCM offers a promising therapeutic strategy for T2DM, and further provide valuable insights into potential probiotic candidates (such as Bacteroidetes spp., Akkermansia spp., and Parabacteroides spp.) and newly identified functional pathways (such as chondroitin sulfate degradation, geraniol degradation, biotin biosynthesis, colonic acid building blocks biosynthesis, and the biosynthesis of vancomycin group antibiotics) that could be targeted for therapeutic intervention.

Diabetes is the third most common chronic disorder worldwide. Diabetic wounds are a severe complication that is costly and often results in non-traumatic lower limb amputation. Recent investigations have demonstrated that the gut microbiota as a "virtual organ" can regulate metabolic diseases like diabetes. Fecal microbiota transplantation (FMT) is an innovative therapeutic approach for promoting wound healing, but its function remains incompletely defined. A diabetes model was established by supplying mice with a high-fat diet and performing an intraperitoneal injection of streptozotocin. Diabetic wounds were then created, followed by bacterial transplantation. The relevant indexes of wound healing were evaluated to verify the promoting effect of FMT on the diabetic wounds. Human skin keratinocytes were also cultured, and cell scratch experiments were conducted to further investigate the underlying mechanism. The FMT regulated the levels of specific bacteria in the diabetic mice and helped restore the balance of intestinal microbes. This transplantation also enhanced wound healing in the diabetic mice by augmenting the closure rate, accelerating re-epithelialization, and boosting collagen deposition in skin wounds. Furthermore, FMT promoted the production of IL-17A, which significantly enhanced the growth and movement of human keratinocytes. Inhibiting molecules related to the IL-17A-mTOR-HIF1α signaling axis were shown to hinder wound re-epithelialization.This study clarifies the function of the IL-17A-mTOR-HIF1α signaling axis in the utilization of FMT in diabetic wound healing, providing a new therapeutic method and target for promoting the healing of diabetic wounds.

The Intestinal microbiota, as the organ with the largest number of microorganisms in the body, plays a crucial role in the physiological functions of the human body. Normal microbiota can be involved in various functions such as energy absorption, metabolism, and immunity of the body, and microbiota imbalance is related to many diseases such as obesity and diabetes. Diabetes, as one of the world's three major chronic diseases, is a significant health issue that troubles more than a billion people globally. Diabetic wounds are a problem that all diabetic patients must confront when undergoing surgery, and it is an important cause of non-traumatic amputations. Exploring the role of intestinal microorganisms in the wound-healing process of diabetic mice can offer the possibility of using microorganisms as a therapeutic means to intervene in clinically related diseases.

Diabetes mellitus (DM), characterized by hyperglycemia, is intricately linked with cardiovascular complications. Hyperglycemia induces oxidative stress, compromising mitochondria energy metabolism disturbances, leading to cardiomyocyte hypoxia and dysregulation of hypoxia-inducible factor-1α (HIF-1α), thereby exacerbating diabetic myocardial injury. Roxadustat (FG-4592), as an inhibitor of HIF-PHD, reduces HIF-1α degradation and regulates the transcription and function of downstream target genes. This study explores the protective effect of FG-4592 on the diabetic myocardium and further investigates the specific mechanisms responsible for this action.

We established diabetic myocardial injury mice and high glucose-induced rat cardiomyocyte models, administered FG-4592 pretreatment to clarify the protective effects and related mechanisms of FG-4592 on diabetic myocardial injury by detecting changes in oxidative stress, mitochondrial function, and related pathways.

FG-4592 demonstrated cardioprotective effects in diabetic mice by regulating mitochondrial structure and function, as well as maintaining oxidative stress balance in the myocardium. It stabilized HIF-1α, activated UCP2, and enhanced the PI3K/AKT/Nrf2 pathway, reducing mitochondrial superoxide production, improving mitochondrial respiratory potential, and modulating oxidative stress markers in high glucose-induced cardiomyocytes.

FG-4592 exerts protective effects against diabetic myocardial injury by reducing oxidative stress. The mechanism is linked with the upregulation of HIF-1α and UCP2, which subsequently activate the PI3K/AKT/Nrf2 signaling pathway.

Type 2 diabetes mellitus (T2DM) is the fastest-growing metabolic disease in the world. The gut microbiota is linked to T2DM. Recent studies have showed that the metabolism of gut microbiota can trigger T2DM. Low dose radiation (LDR) has been proved to activate various protective bioeffects on diabetes. However, the underlying mechanisms remain unclear.

In this study, T2DM model was established using high fat diet combined with streptozocin (STZ) injection in C57BL/6 mice, and then exposed to multiple 75 mGy LDR every other day for one month. The changes of blood glucose levels, body weight, and the damage of pancreas were measured. In addition, 16 S rDNA amplicon sequencing was used to detect gut microbiota alteration. Metabolic profiling was carried out using the liquid mass spectrometry system, followed by the combinative analysis of gut microbiota alteration. Furthermore, the inflammatory factors and related pathways were detected.

We found that LDR attenuate blood glucose levels and the weights of body in T2DM mice, and reduce pancreas impairment. In addition, in the gut, LDR regulated the relative abundance of Bacilli, Desulfobacterota, Verrucomicrobiota, and Proteobacteria. The non-target metabolomics analysis found that LDR significantly improve the metabolic abnormalities in T2DM, which is closely related to the gut microbiota abundance. Furthermore, the inflammatory effects activated by TLR4/MyD88/NF-κB pathways in T2DM were ameliorated by LDR.

These results suggest that LDR may exert a beneficial role in T2DM by modulating gut microbiota and metabolites, especially in TLR4/MyD88/NF-κB pathway.

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, and its pathogenesis remains incompletely understood. Emerging evidence suggests a potential link between gut microbiota and DN. This study aimed to explore the causal relationship between gut microbiota and DN using a two-sample Mendelian randomization (MR) approach.

Gut microbiota data were obtained from the MiBioGen consortium, which provides the most comprehensive genome-wide association studies (GWAS) on gut microbiota. Summary-level genetic data for DN were sourced from publicly available GWAS data provided by the FinnGen consortium. The primary analysis was conducted using the inverse variance-weighted (IVW) method, complemented by sensitivity analyses to evaluate pleiotropy and heterogeneity.

Fourteen gut microbiota species demonstrated significant genetic associations with DN in the MR analysis, including five negatively and nine positively associated species, as determined by the IVW method. No evidence of pleiotropy or heterogeneity was observed, ensuring the robustness of the findings.

This study provides novel insight into the causal role of gut microbiota in DN pathogenesis, uncovering specific microbial species that may contribute to disease progression. These findings offer a promising avenue for future research and therapeutic development targeting gut microbiota.

Indole-3-carbinol (I3C) is a compound derived from Cruciferous vegetables. We aim to ascertain whether I3C mediates the relations between mouse gut microbiota, intestinal barrier function, and metabolism to treat obesity in mice.

The experimental analyses focused on the changes in lipid distribution, inflammatory cytokines, glucose tolerance, gut microbiota composition, and serum metabolomics of 60 C57BL/6N mice.

The experimental results demonstrated that I3C reduced body weight, hepatic steatosis, and systemic inflammation and improved insulin resistance in mice on a high-fat diet (HFD). Furthermore, I3C remarkably enhanced the enrichment of probiotics Akkermansia and Ligilactobacillus as well as SCFA-producing bacteria (Eubacterium, Lactococcus, and Coprococcus), while reducing the abundance of Eisenbergiella and Rikenellaceae_RC9_gut_group. Also, I3C notably up-regulated the levels of Claudin4, Occludin, and ZO-1 proteins and modulated the metabolism of argininosuccinic acid and galactose.

The aforementioned findings suggest that I3C exerts a significant anti-obesity effect in mice by regulating abnormal gut microbiome, enhancing intestinal barrier function, and improving metabolic disorders.

Grifola frondosa polysaccharide (GFP) has a positive effect in regulating type 2 diabetes mellitus (T2DM), but the understanding of its regulatory mechanism is still limited. Accumulating evidence suggests that hepatic inflammation is crucial in the onset and progression of insulin resistance (IR) and T2DM. However, the question of whether GFP can modulate T2DM via regulating hepatic inflammation and the underlying mechanism has not yet been reported.

High-fat diet (HFD) fed combined with streptozocin (STZ) injections rat model and Lipopolysaccharides (LPS)-treated bone marrow-derived macrophages (BMDM) model are used. The results showed that GFP intervention reduces weight loss and hyperglycemia symptoms, besides lowers FINS, HOMA-IR, IPGTT-AUC, and IPITT-AUC in T2DM rats. Meanwhile, GFP intervention reduces the secretion level of inflammatory factors and increases the secretion level of anti-inflammatory factors in the liver tissue of T2DM rats. Furthermore, GFP reduces macrophage infiltration in liver tissue, inhibits macrophage M1-type polarization, and promotes M2-type polarization.

These results suggest that GFP intervention could attenuate the hepatic inflammatory and insulin resistance in T2DM rats by inhibiting hepatic macrophage infiltration and modulating M1/M2 polarization. The findings provide new evidence for GFP in the early prevention and treatment of T2DM.

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, influenced by dietary and environmental factors that can modify the intestinal microbiota. The aim of this study was to evaluate changes in the composition and diversity of the intestinal microbiota associated with carbohydrate (CHO) consumption in T2DM patients. Forty patients participated, with and without T2DM. Fecal samples were collected for the characterization of microbial diversity from the massive sequencing of the 16S rRNA gene. Carbohydrate consumption was quantified using the Frequency Consumption Foods questionnaire (FCF), the groups were categorized according to Body Mass Index (BMI) and BMI + CHO consumption. The group without T2DM showed normal biochemical and anthropometric parameters, although they had a high carbohydrate consumption compared to the group with T2DM. At the phylum level, there were differences in relative abundance; the control overweight group (CL-OW > CHO) and T2DM-Normal Weight > CHO patients had increased Bacteroides and decreased Firmicutes. In contrast, the CL-OW > CHO and T2DM-OW < CHO patients, showed reduced Bacteroidetes and an elevated amount of Firmicutes. At the genus level, the differences were in the relative abundance of Roseburia, Clostridium_IV, Prevotella, and Sporobacter, associated with the consumption of carbohydrates. The groups that consumed high amounts of carbohydrates, regardless of whether they had diabetes mellitus or were overweight, had a significantly reduced proportion of Faecalibacterium, an altered proportion of Bacteroides. The high consumption of carbohydrates showed considerable modifications in the composition and diversity of the bacterial communities.

Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance and inadequate insulin production. Given the increased frequency of T2DM and the health issues it can cause, there is an increasing need to develop alternative T2DM management strategies. One such approach is Chinese Medicine (CM), a complementary therapy widely used in T2DM treatment. Given the emphasis on gut microbiota in current research, studying CM in the treatment of T2DM via gut microbiota modulation could be beneficial. Scope and approach: The use of various CM methods for managing T2DM via gut microbiota modulation is highlighted in this review. Following an introduction of the gut microbiota and its role in T2DM pathogenesis, we will review the potential interactions between gut microbiota and T2DM. Thereafter, we will review various CM treatment modalities that modulate gut microbiota and provide perspectives for future research. Key findings and discussion: In T2DM, Akkermansia, Bifidobacterium, and Firmicutes are examples of gut microbiota commonly imbalanced. Studies have shown that CM therapies can modulate gut microbiota, leading to beneficial effects such as reduced inflammation, improved metabolism, and improved immunity. Among these treatment modalities, Chinese Herbal Medicine and acupuncture are the most well-studied, and several in vivo studies have demonstrated their potential in managing T2DM by modulating gut microbiota. However, the underlying biomolecular mechanisms of actions are not well elucidated, which is a key area for future research. Future studies could also investigate alternate CM therapies such as moxibustion and CM exercises and conduct large-scale clinical trials to validate their effectiveness in treatment.

We aimed to assess temporal trends in type 2 diabetes mellitus (T2DM)-related deaths and disability-adjusted life years (DALYs) at global and cross-social demographic index (SDI) levels, using data from the Global Burden of Disease (GBD) in 2021.

We used geospatial mapping to visualize the global distribution of T2DM-related mortality and DALYs in 2021. Joinpoint regression assessed annual and average percent changes in DALYs and deaths from 1990 to 2021 across SDI regions. Age-period-cohort modeling examined the effects of age, period, and cohort on trends. Decomposition analysis evaluated the impact of population growth, aging, and epidemiological changes on DALY trends. A stratified projection forecasted future T2DM burden by age and sex from 2020 to 2044.

T2DM-related mortality and DALYs were highest in low-SDI regions. Globally, T2DM-related deaths and DALYs have increased, with the most rapid rise in low and low-middle SDI regions, driven by population growth and epidemiological shifts. High-SDI countries showed a slower increase in DALYs, influenced more by aging. Age-period-cohort analysis indicated higher DALY rates in later birth cohorts and recent periods, especially in high-SDI regions. Future projections show a significant increase in the 70-74 age group and a gradual rise in other age groups.

The burden of T2DM is projected to continue increasing, especially in low-SDI and low-middle SDI regions, where population growth and epidemiological shifts are the main contributors. This underscores the need for targeted, region-specific healthcare policies, preventive strategies, and age-specific interventions to address the increasing T2DM burden globally.

Introduction: Microbiota, composed of micro-organisms like bacteria, viruses, and non-pathogenic fungi, plays a crucial role in digestion, vitamin production, and protection against dangerous microbes. Several factors, including age, diet, alcohol consumption, stress, environmental microorganisms, and therapies (particularly antibiotics), as well as birth and nursing, could modify the microbiota. Recent research has highlighted its alteration and involvement in a various disease, including metabolic syndrome and acne. This systematic review aimed to identify common biomarkers and microbiota alterations shared between metabolic syndrome and acne, and to explore how the potential prebiotic activities of polyphenols may promote intestinal eubiosis. Materials and methods: A comprehensive search in PubMed and EMBASE resulted in 4142 articles, from which nine studies were selected based on specific criteria after removing duplicates and reviewing abstracts and full texts. All studies correlated the microbiota alteration in both pathologies and the activity of polyphenols in metabolic syndrome. Results: This review suggests that acne may be influenced by some of the same microorganisms involved in metabolic syndrome. While the literature highlights the effectiveness of polyphenols in treating metabolic syndrome, no studies have yet demonstrated their specific impact on acne. Conclusions: The research points to the potential benefits of polyphenols in modulating the microbiota, which could be relevant for individuals with metabolic syndrome. However, due to the limited data available, it was not possible to establish a direct correlation between metabolic syndrome and acne.

Metformin, an anti-diabetic drug, regulates blood glucose by affecting gut microbiotas. However, the potential mechanism underlying this effect remains unclear. This study aimed to evaluate the effect of metformin on glucose regulation, lipid levels, and the gut microbiota in rats with type 2 diabetes mellitus induced by a high-fat diet with streptozotocin.

Thirty Wistar rats was using in this experiment. T2DM rats were administered 300 mg/kg metformin for 8 weeks. The glucose regulation, lipid levels, organ coefficients, and gut microbiotawere measured by 16S rDNA.

The metformin-gavaged rats exhibited significant improvements in blood glucose and serum lipid levels, accompanied by alterations in short-chain fatty acid levels and the intestinal microbiota (p < 0.05). In the diabetic rats, metformin potentially increased specific probiotics, thus improving the hypoglycaemic effects of the oral anti-diabetic drug. Further, damage to the liver and kidney was effectively alleviated in the metformin-gavaged rats.

This study's findings demonstrate that metformin exerts a positive anti-diabetic effect in HFD- and STZ-induced T2DM rats. These findings potentially provide a basis for the recommended use of metformin as a reliable oral drug for T2DM owing to its positive effect on the intestinal microbiota.

Obesity and related complications are managed by One Anastomosis Gastric Bypass (OAGB) and Single Anastomosis Duodeno-Jejunal Bypass with Sleeve Gastrectomy (SADJB-SG), both of which are adapted from traditional gastric bypass procedures. However, there are no current comparative studies on the safety and efficacy of these two surgical procedures.

Preoperative baseline data of patients who had undergone OAGB and SADJB-SG surgeries from June 2019 to June 2021 were retrospectively analyzed at our bariatric facility. Postoperative data, including weight changes, improvement in type 2 diabetes (T2DM), and complication rates were collected over 2 years. This was followed by a comprehensive evaluation of the safety and efficacy of the two surgical procedures.

A total of 63 patients completed the follow-up in this study. At the 24-month follow-up, excess weight loss percentage (EWL%) for the OAGB and SADJB-SG was 73.970±5.005 and 75.652±7.953, respectively (P-value = 0.310); total weight loss percentage (TWL%) was 24.006±8.231 and 23.171±6.600, respectively (P-value = 0.665). The diabetes remission rates for the two groups were 71.429% and 69.048%, respectively (P-value = 0.846). The cost for OAGB was 55088.208±1508.220 yuan, which was significantly lower than the 57538.195±1374.994 yuan for SADJB-SG (P-value< 0.001).

The two surgical procedures are reliable in terms of safety and efficacy, and each has distinct advantages. While OAGB has reduced operational expenses, SADJB-SG offers a broader range of applicability.

The metabolic disorder Type 2 Diabetes Mellitus (T2DM) is characterized by hyperglycaemia, causing increased mortality and healthcare burden globally. Recent studies emphasize the impact of metabolites in the gut microbiome on T2DM pathogenesis. One such microbial metabolite, imidazole propionate (Imp) derived from histidine metabolism, is shown to interfere with insulin signalling and other key metabolic processes. The key enzyme urocanate reductase (UrdA) is involved in ImP production. Hence, we propose to develop a novel therapeutic vaccine against the gut microbe producing Imp based on UrdA as a target for treating T2DM using immunoinformatics approach. Antigenic, non-allergic, non-toxic, and immunogenic B cell and T cell potential epitopes were predicted using immunoinformatics servers and tools. These epitopes were adjoined using linker sequences, and to increase immunogenicity, adjuvants were added at the N-terminal end of the final vaccine construct. Further, to confirm the vaccine's safety, antigenic and non-allergic characteristics of the developed vaccine construct were assessed. The tertiary structure of the UrdA vaccine sequence was predicted using molecular modelling tools. A molecular docking study was utilized to understand the vaccine construct interaction with immune receptors, followed by molecular dynamics simulation and binding free energy calculations to assess stability of the complex. In silico cloning techniques were employed to evaluate the expression and translation effectiveness of the developed vaccine in pET vector. In conclusion, this study developed an in silico epitope-based vaccine construct as a novel adjunct therapeutic for T2DM.

Random-pattern skin flaps are commonly used to repair skin tissue defects in surgical tissue reconstruction. However, flap necrosis in the distal area due to ischemia injury is still challenging for its applications in plastic surgery. The complications of diabetes will further increase the risk of infection and necrosis.

This study induced type 2 diabetes mellitus (T2DM) rats with a high-fat diet and STZ. The survival rate of the skin flap was observed by adding inorganic sodium nitrate to drinking water. Histology and immunohistochemistry were used to detect the damage to the skin flap. The nitrate content was measured by total nitric oxide and nitrate/nitrite parameter assay. Dihydroethidium and malondialdehyde (MDA) assays were used to value oxidative stress. Rat colon feces were collected for 16s rRNA gene sequence.

Our studies showed that nitrate administration leads to anti-obesity and anti-diabetic effects. Nitrate directly increased the survival area of skin flaps in diabetic rats and mean blood vessel density by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. The 16s rRNA sequence revealed that nitrate may regulate the homeostasis of the gut microbiota and re-store energy metabolism.

Dietary nitrate has been shown to maintain the homeostasis of oxidative stress and gut microbiota to promote flap survival in rats with T2DM.

The adzuki bean is a mature seed of the red bean leguminous plant, and people like to eat it because of its nutritious properties and moderate proportion of amino acids. Adzuki bean germination and the enrichment of GABA greatly improve the health effects of the adzuki bean. The effects of the GABA-rich adzuki bean on the expression of insulin-pathway-related genes and proteins in the liver of T2DM mice were studied via Western blotting and qPCR. The results showed that a GABA-rich adzuki bean diet could promote glycogen synthesis in the liver of T2DM mice, inhibit the activities of PEPCK and G-6-Pase, and significantly down-regulate the gene expression levels of PEPCK, G6PC and FOXO1 (p < 0.05) and the phosphorylation levels of FOXO1 and GSK3β. In addition, it can also up-regulate the expression of the AMPKα gene and down-regulate the expression of the SREBP1c gene to inhibit the synthesis of triglycerides and cholesterol in T2DM mice. Lipid accumulation in mice can alleviate glucose and lipid metabolism disorders and play an effective role in regulating blood glucose at liver tissue targets. This study suggested that the GABA-rich adzuki bean can improve hyperglycemia in type 2 diabetic mice by activating the IRS/PI3K/AKT signaling pathway in the liver.

In this study, we aimed to explore the hypoglycemic effects of a hydrolysate on Takifugu bimaculatus skin (TBSH). The effect of the dipeptidyl peptidase-IV (DPP-IV) inhibitory activities from different TBSH fractions was investigated on basic indexes, gut hormones, blood lipid indexes, viscera, and the gut microbiota and its metabolites in rats with type 2 diabetes mellitus (T2DM). The results showed that the <1 kDa peptide fraction from TBSH (TBP) exhibited a more potent DPP-IV inhibitory effect (IC50 = 0.45 ± 0.01 mg/mL). T2DM rats were induced with streptozocin, followed by the administration of TBP. The 200 mg/kg TBP mitigated weight loss, lowered fasting blood glucose levels, and increased insulin secretion by 20.47%, 25.23%, and 34.55%, respectively, rectified irregular hormonal fluctuations, lipid metabolism, and tissue injuries, and effectively remedied gut microbiota imbalance. In conclusion, TBP exerts a hypoglycemic effect in rats with T2DM. This study offers the potential to develop nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus. It will provide information for developing nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus.

Gegen Qinlian Decoction (GGQLT) is a traditional Chinese herbal medicine that has been reported to have a significant therapeutic effect in the management of type II diabetes mellitus (T2DM). In this study, we constructed a T2DM rat model by feeding a high-fat diet and injecting streptozotocin (STZ) and tested the effects of feeding GGQLT and fecal transplantation on the physiological indices, microbiota, and metabolism of rats. The results showed that the administration of GGQLT can significantly improve the growth performance of rats and has a remarkable antihyperlipidemic effect. In addition, GGQLT altered the composition of gut microbiota by increasing beneficial bacteria such as Coprococcus, Bifidobacterium, Blautia, and Akkermansia. In addition, GGQLT elevated levels of specific bile acids by metabolomic analysis, potentially contributing to improvements in lipid metabolism. These findings suggest that GGQLT may have beneficial effects on T2DM by influencing lipid metabolism and gut microbiota. However, further studies are needed to elucidate its mechanisms and assess clinical applications.

Non-alcoholic fatty liver disease stands as the predominant cause of chronic liver disease, with its prevalence and morbidity expected to escalate significantly, leading to substantial healthcare costs and diminished health-related quality of life. It comprises a range of disease manifestations that commence with basic steatosis, involving the accumulation of lipids in hepatocytes, a distinctive histological feature. If left untreated, it often advances to non-alcoholic steatohepatitis, marked by inflammatory and/or fibrotic hepatic changes, leading to the eventual development of non-alcoholic fatty liver disease-related cirrhosis and hepatocellular carcinoma. Because of the liver's vital role in body metabolism, non-alcoholic fatty liver disease is considered both a consequence and a contributor to the metabolic abnormalities observed in the metabolic syndrome. As of date, there are no authorized pharmacological agents for non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Semaglutide, with its glycemic and weight loss advantages, could potentially offer benefits for individuals with non-alcoholic fatty liver disease. This review aims to investigate the impact of semaglutide on non-alcoholic fatty liver disease.

Morchella importuna polysaccharide (MIP) has been proven to have obvious hypoglycemic effects on mice with type 2 diabetes (T2DM). This study looked at the functional and rheological characteristics of MIP, and investigated the effects of MIP on the human fecal microbiota through in vitro fermentation experiments. The outcomes demonstrate the excellent oil-holding capacity, emulsifying, foaming, and rheological characteristics of MIP. After salivary gastrointestinal digestion, the Mw of MIP decreased from 398.2 kDa and 21.5 kDa to 21.9 kDa and 11.7 kDa. By 16S rRNA sequencing of bacteria fermented in vitro, it was found that MIP did not improve the richness and diversity of intestinal microorganisms, but it may exert an anti-T2DM function by significantly increasing the relative abundance of Firmicutes and promoting Ruminococcaceae_UCG_014, Bacteroides, and Blautia proliferation. Escherichia-Shigella could also be inhibited to improve the intestinal microenvironment. In addition, the fermentation of MIP increased the total short-chain fatty acid (SCFA) concentration from 3.23 mmol/L to 39.12 mmol/L, and the propionic acid content increased significantly. In summary, MIP has excellent processing performance and is expected to exert potential anti-T2DM activity through the human intestinal microbiota, which has broad market prospects.

This study examined the effects of tocotrienols (TT) in conjunction with statin on glucose homeostasis, bone microstructure, gut microbiome, and systemic and liver inflammatory markers in obese C57BL/6J mice.

Forty male C57BL/6J mice were fed a high-fat diet (HFD) and assigned into four groups in a 2 (no statin vs. 120 mg statin/kg diet)×2 (no TT vs. 400 mg TT/kg diet) factorial design for 14 weeks.

Statin and TT improved glucose tolerance only when each was given alone, and only statin supplementation decreased insulin resistance. Consistently, only statin supplementation decreased serum insulin levels and HOMA-IR. Pancreatic insulin was also increased with statin treatment. Statin and TT, alone or in combination, reduced the levels of serum IL-6, but only TT attenuated the increased serum leptin levels induced by a HFD. Statin supplementation increased bone area/total area and connectivity density at LV-4, while TT supplementation increased bone area/total area and trabecular number, but decreased trabecular separation at the distal femur. Statin supplementation, but not TT, reduced hepatic inflammatory cytokine gene expression. Neither TT supplementation nor statin supplementation statistically altered microbiome species evenness or richness. However, they altered the relative abundance of certain microbiome species. Most notably, both TT and statin supplementation increased the relative abundance of Lachnospiraceae UCG-006.

TT and statin collectively benefit bone microstructure, glucose homeostasis, and microbial ecology in obese mice. Such changes may be, in part, associated with suppression of inflammation in the host.

Type 2 diabetes mellitus (T2DM) is a burgeoning public health challenge worldwide. Individuals with T2DM are at increased risk for skeletal muscle atrophy, a serious complication that significantly compromises quality of life and for which effective prevention measures are currently inadequate. Emerging evidence indicates that systemic and local inflammation stemming from the compromised intestinal barrier is one of the crucial mechanisms contributing to skeletal muscle atrophy in T2DM patients. Notably, natural plant polysaccharides were found to be capable of enhancing intestinal barrier function and mitigating secondary inflammation in some diseases. Herein, we hypothesized that Grifola frondosa polysaccharide (GFP), one of the major plant polysaccharides, could prevent skeletal muscle atrophy in T2DM via regulating intestinal barrier function and inhibiting systemic and local inflammation. Using a well-established T2DM rat model, we demonstrated that GFP was able to not only prevent hyperglycemia and insulin resistance but also repair intestinal mucosal barrier damage and subsequent inflammation, thereby alleviating the skeletal muscle atrophy in the T2DM rat model. Additionally, the binding free energy analysis and molecular docking of monosaccharides constituting GFP were further expanded for related targets to uncover more potential mechanisms. These results provide a novel preventative and therapeutic strategy for T2DM patients.

Type 2 diabetes (T2DM) significantly diminishes people's quality of life and imposes a substantial economic burden. This pathological progression is intimately linked with specific gut microbiota, such as Akkermansia muciniphila. Pasteurized A. muciniphila (P-AKK) has been defined as a novel food by the European Food Safety Authority and exhibited significant hypoglycemic activity. However, current research on the hypoglycemic activity of P-AKK is limited to the metabolic level, neglecting systematic exploration at the pathological level. Consequently, its material basis and mechanism of action for hypoglycemia remain unclear. Drawing upon this foundation, we utilized high-temperature killed A. muciniphila (H-K-AKK) with insignificant hypoglycemic activity as the control research object. Assessments were conducted at pathological levels to evaluate the hypoglycemic functions of both P-AKK and H-K-AKK separately. Our study unveiled for the first time that P-AKK ameliorated symptoms of T2DM by enhancing the generation of glucagon-Like Peptide 1 (GLP-1), with pasteurized A. muciniphila total proteins (PP) being a pivotal component responsible for this activity. Utilizing SDS-PAGE, proteomics, and molecular docking techniques, we deeply analyzed the material foundation of PP. We scientifically screened and identified a protein weighing 77.85 kDa, designated as P5. P5 enhanced GLP-1 synthesis and secretion by activating the G protein-coupled receptor (GPCR) signaling pathway, with free fatty acid receptor 2 (FFAR-2) being identified as the pivotal target protein for P5's physiological activity. These findings further promote the widespread application of P-AKK in the food industry, laying a solid theoretical foundation for its utilization as a beneficial food ingredient or functional component.

Gut microbiome (GM) and type 2 diabetes mellitus (T2DM) have two-way effects. Improving T2DM by modulating GM in various ways, such as diet, exercise, and medication, is gradually becoming popular, and related studies have yielded positive results. However, there is still a lack of high-quality bibliometric analyses of research in this area. This study aims to systematize and comprehensively summarize the knowledge structure, research tropics, and research trends of GM and T2DM through bibliometric analysis.

Publications related to GM and T2DM before January 9, 2024, in the Web of Science Core Collection (WOSCC) were searched in this study. Microsoft Excel 2019 was used to analyze publishing trends and CiteSpace (v.6.1.R6 Advanced) was used to analyze institutions, cited journals, references, and keywords.SCImago Graphica (v.1.0.39) was used to analyze countries/regions, institutions' collaborations, cited authors, and published journals.

We finally included 1004 articles published from 2008 to 2023. The number of published articles showed an upward trend and reached its peak in 2022. China is the country with the largest number of articles, Univ Copenhagen is the institution with the largest number of articles, Fukui, Michiaki, Hamaguchi, Masahide are the scholars with the largest number of articles, and Cani and Patrice D. are the scholars with the largest number of citations. NUTRIENTS(Q1/5.9) published the most publications, while Nature (Q1/64.8; Cited 804 times) is the most frequently cited journal. Gut microbiota, Obesity, and insulin resistance are the most frequently used keywords. This study found that current researches focus on the effects of diet, exercise, and pharmacological modification of GM to improve T2DM and explores specific mechanisms. Future researches will focus on three areas: complications of T2DM and specific physiological processes, methods and measures to regulate GM, and new experimental techniques and assays.

The current researches confirmed the effects and specific mechanisms of modulating GM to improve T2DM. Further exploration of the effects of modulating GM on T2DM complications and specific physiologic processes is a future trend of research. Exploring specific methods for regulating GM and developing new experimental techniques and assays are important for future research.

Pravastatin is an oral lipid-lowering drug, commonly used by patients with diabetes that is positively correlated with the occurrence of vascular calcification (VC), but the mechanism is unclear.

In this study, 16S rRNA sequencing and qRT-PCR wereused to detect the differential gut bacteria. Metabolomics and ELISA were used to analyze the differential metabolites. qRT-PCR and western blotting (WB) were used to detect genes expression. Flow cytometry was used to analyze macrophage phenotype. Immunohistochemistry was used to analyze aortic calcification.

We found that gut Bacteroides fragilis (BF) increased significantly in patients who took pravastatin or type 2 diabetes (T2D) mice treated with pravastatin. In vitro experiments showed that pravastatin had little effect on BF but significantly promoted BF proliferation in vivo. Further analysis showed that ArsR was an important gene for pravastatin to regulate the activation of BF, and overexpression of ArsR significantly promoted the secretion of 3,4,5-trimethoxycinnamic acid (TMCA). Importantly, pravastatin significantly promoted BF secretion of TMCA and significantly increased TMCA secretion in T2D patients or T2D mice. TMCA had little effect on vascular smooth muscle cell calcification but significantly promoted macrophage M1 polarization, which we had demonstrated that M1 macrophages promoted T2D VC. In vivo studies found that pravastatin significantly upregulated TMCA levels in the feces and serum of T2D mice transplanted with BF and promoted the macrophage M1 polarization in bone marrow and the osteoblastic differentiation of aortic cells. Similar results were obtained in T2D mice after intravenous infusion of TMCA.

Promoting intestinal BF to secrete TMCA, which leads to macrophage M1 polarization, is an important mechanism by which pravastatin promotes calcification, and the result will be used for the optimization of clinical medication strategies of pravastatin supplying a theoretical basis and experimental basis.

This review delves into the complex interplay between obesity-induced gut microbiota dysbiosis and the progression of type 2 diabetes mellitus (T2DM), highlighting the potential of natural products in mitigating these effects. By integrating recent epidemiological data, we aim to provide a nuanced understanding of how obesity exacerbates T2DM through gut flora alterations.

Advances in research have underscored the significance of bioactive ingredients in natural foods, capable of restoring gut microbiota balance, thus offering a promising approach to manage diabetes in the context of obesity. These findings build upon the traditional use of medicinal plants in diabetes treatment, suggesting a deeper exploration of their mechanisms of action. This comprehensive manuscript underscores the critical role of targeting gut microbiota dysbiosis in obesity-related T2DM management and by bridging traditional knowledge with current scientific evidence; we highlighted the need for continued research into natural products as a complementary strategy for comprehensive diabetes care.

Probiotics have garnered increasing attention as a potential therapeutic approach for type 2 diabetes mellitus (T2DM). Previous studies have confirmed that Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) could stimulate the secretion of glucagon-like peptide-1 (GLP-1) in NCI-H716 cells, but whether MN-Gup has a hypoglycemic effect on T2DM in vivo remains unclear. In this study, a T2DM mouse model was constructed, with a high-fat diet and streptozotocin in mice, to investigate the effect of MN-Gup on diabetes. Then, different doses of MN-Gup (2 × 109 CFU/kg, 1 × 1010 CFU/kg) were gavaged for 6 weeks to investigate the effect of MN-Gup on glucose metabolism and its potential mechanisms. The results showed that a high-dose of MN-Gup significantly reduced the fasting blood glucose (FBG) levels and homeostasis model assessment-insulin resistance (HOMA-IR) of T2DM mice compared to the other groups. In addition, there were significant increases in the short-chain fatty acids (SCFAs), especially acetate, and GLP-1 levels in the MN-Gup group. MN-Gup increased the relative abundance of Bifidobacterium and decreased the number of Escherichia-Shigella and Staphylococcus. Moreover, the correlation analysis revealed that Bifidobacterium demonstrated a significant positive correlation with GLP-1 and a negative correlation with the incremental AUC. In summary, this study demonstrates that Bifidobacterium animalis subsp. lactis MN-Gup has significant hypoglycemic effects in T2DM mice and can modulate the gut microbiota, promoting the secretion of SCFAs and GLP-1.