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In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis. Proc Natl Acad Sci U S A 2020; 117:2484-2495. [PMID: 31964806 PMCID: PMC7007532 DOI: 10.1073/pnas.1916539117] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Circadian clocks operative in pancreatic islets participate in the regulation of insulin secretion in humans and, if compromised, in the development of type 2 diabetes (T2D) in rodents. Here we demonstrate that human islet α- and β-cells that bear attenuated clocks exhibit strongly disrupted insulin and glucagon granule docking and exocytosis. To examine whether compromised clocks play a role in the pathogenesis of T2D in humans, we quantified parameters of molecular clocks operative in human T2D islets at population, single islet, and single islet cell levels. Strikingly, our experiments reveal that islets from T2D patients contain clocks with diminished circadian amplitudes and reduced in vitro synchronization capacity compared to their nondiabetic counterparts. Moreover, our data suggest that islet clocks orchestrate temporal profiles of insulin and glucagon secretion in a physiological context. This regulation was disrupted in T2D subjects, implying a role for the islet cell-autonomous clocks in T2D progression. Finally, Nobiletin, an agonist of the core-clock proteins RORα/γ, boosted both circadian amplitude of T2D islet clocks and insulin secretion by these islets. Our study emphasizes a link between the circadian clockwork and T2D and proposes that clock modulators hold promise as putative therapeutic agents for this frequent disorder.
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Dibner C. The importance of being rhythmic: Living in harmony with your body clocks. Acta Physiol (Oxf) 2020; 228:e13281. [PMID: 30980501 DOI: 10.1111/apha.13281] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 04/05/2019] [Accepted: 04/08/2019] [Indexed: 02/06/2023]
Abstract
Circadian rhythms have developed in all light-sensitive organisms, including humans, as a fundamental anticipatory mechanism that enables proactive adaptation to environmental changes. The circadian system is organized in a highly hierarchical manner, with clocks operative in most cells of the body ensuring the temporal coordination of physiological processes. Circadian misalignment, stemming from modern life style, draws increasing attention due to its tight association with the development of metabolic, cardiovascular, inflammatory and mental diseases as well as cancer. This review highlights recent findings emphasizing the role of the circadian system in the temporal orchestration of physiology, with a particular focus on implications of circadian misalignment in human pathologies.
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Affiliation(s)
- Charna Dibner
- Division of Endocrinology, Diabetes, Hypertension and Nutrition, Department of Medicine University Hospital of Geneva Geneva Switzerland
- Department of Cell Physiology and Metabolism, Faculty of Medicine University of Geneva Geneva Switzerland
- Diabetes Center, Faculty of Medicine University of Geneva Geneva Switzerland
- Institute of Genetics and Genomics in Geneva (iGE3) Geneva Switzerland
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3
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Fang S, Zhou J. Association of Daytime Napping and Diagnosed Diabetes in Middle-Aged Premenopausal, Middle-Aged Postmenopausal, and Older Postmenopausal Chinese Women. Am J Health Promot 2019; 33:1107-1114. [PMID: 31167538 DOI: 10.1177/0890117119854918] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE To examine associations of daytime napping and diagnosed diabetes in middle-aged premenopausal, middle-aged postmenopausal, and older postmenopausal Chinese women. DESIGN Quantitative, cross-sectional. SETTING 2015 cross-sectional data from China Health and Retirement Longitudinal Study. Participants were recruited from 150 counties/districts and 450 villages/resident committees. PARTICIPANTS Six thousand nine hundred and forty women aged 45 years and older (mean age = 61 years) stratified by age and menopausal status. MEASURES The outcome was self-reported diagnosed diabetes. The exposure was self-reported daytime napping (0, >0-≤60, or >60 min/d). Participants were stratified to middle-aged premenopausal, middle-aged postmenopausal, and older postmenopausal women according to their age (≤60 or >60 years) and menopausal status. ANALYSIS One-way analysis of variance and χ2 tests were conducted to explore differences on characteristics of middle-aged premenopausal, middle-aged postmenopausal, and older postmenopausal women. Multiple logistic regressions were used to estimate adjusted odds ratios (ORs) for diagnosed diabetes according to daytime napping in the total sample, middle-aged premenopausal, middle-aged postmenopausal, and older postmenopausal Chinese women. RESULTS Participants' mean self-reported daytime napping duration was 34 minutes. Women who napped more than 60 minutes were more likely to report diagnosed diabetes (OR = 1.39, 95% confidence interval (CI), 1.09-1.76) comparing to those who did not nap, after adjusting for potential confounders. No statistical significance of interaction term between daytime napping and age/menopausal status was detected (P = .602 and P = .558) among total women. The stratified analysis revealed the significant association among middle-aged postmenopausal women napping more than 60 minutes (OR = 1.81, 95% CI, 1.18-2.77). The association, however, was found to be insignificant in middle-aged premenopausal women and older postmenopausal women. CONCLUSIONS Long daytime nap (>60 min/d) was associated with diagnosed diabetes in middle-aged postmenopausal women in China.
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Affiliation(s)
- Shu Fang
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Junmin Zhou
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
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Bae SA, Androulakis IP. Mathematical modeling informs the impact of changes in circadian rhythms and meal patterns on insulin secretion. Am J Physiol Regul Integr Comp Physiol 2019; 317:R98-R107. [PMID: 31042416 DOI: 10.1152/ajpregu.00230.2018] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Disruption of circadian rhythms has been associated with metabolic syndromes, including obesity and diabetes. A variety of metabolic activities are under circadian modulation, as local and global clock gene knockouts result in glucose imbalance and increased risk of metabolic diseases. Insulin release from the pancreatic β cells exhibits daily variation, and recent studies have found that insulin secretion, not production, is under circadian modulation. As consideration of daily variation in insulin secretion is necessary to accurately describe glucose-stimulated insulin secretion, we describe a mathematical model that incorporates the circadian modulation via insulin granule trafficking. We use this model to understand the effect of oscillatory characteristics on insulin secretion at different times of the day. Furthermore, we integrate the dynamics of clock genes under the influence of competing environmental signals (light/dark cycle and feeding/fasting cycle) and demonstrate how circadian disruption and meal size distribution change the insulin secretion pattern over a 24-h day.
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Affiliation(s)
- Seul-A Bae
- Chemical & Biochemical Engineering Department, Rutgers University , Piscataway, New Jersey
| | - Ioannis P Androulakis
- Chemical & Biochemical Engineering Department, Rutgers University , Piscataway, New Jersey.,Biomedical Engineering Department, Rutgers University , Piscataway, New Jersey.,Department of Surgery, Rutgers-Robert Wood Johnson Medical School , New Brunswick, New Jersey
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5
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Kim P, Oster H, Lehnert H, Schmid SM, Salamat N, Barclay JL, Maronde E, Inder W, Rawashdeh O. Coupling the Circadian Clock to Homeostasis: The Role of Period in Timing Physiology. Endocr Rev 2019; 40:66-95. [PMID: 30169559 DOI: 10.1210/er.2018-00049] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 07/06/2018] [Indexed: 01/01/2023]
Abstract
A plethora of physiological processes show stable and synchronized daily oscillations that are either driven or modulated by biological clocks. A circadian pacemaker located in the suprachiasmatic nucleus of the ventral hypothalamus coordinates 24-hour oscillations of central and peripheral physiology with the environment. The circadian clockwork involved in driving rhythmic physiology is composed of various clock genes that are interlocked via a complex feedback loop to generate precise yet plastic oscillations of ∼24 hours. This review focuses on the specific role of the core clockwork gene Period1 and its paralogs on intra-oscillator and extra-oscillator functions, including, but not limited to, hippocampus-dependent processes, cardiovascular function, appetite control, as well as glucose and lipid homeostasis. Alterations in Period gene function have been implicated in a wide range of physical and mental disorders. At the same time, a variety of conditions including metabolic disorders also impact clock gene expression, resulting in circadian disruptions, which in turn often exacerbates the disease state.
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Affiliation(s)
- Pureum Kim
- School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
| | - Henrik Oster
- Institute of Neurobiology, University of Lübeck, Lübeck, Germany
| | - Hendrik Lehnert
- Department of Internal Medicine 1, University of Lübeck, Lübeck, Germany
- German Center for Diabetes Research, Neuherberg, Germany
| | - Sebastian M Schmid
- Department of Internal Medicine 1, University of Lübeck, Lübeck, Germany
- German Center for Diabetes Research, Neuherberg, Germany
| | - Nicole Salamat
- School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
| | - Johanna L Barclay
- Mater Research Institute, University of Queensland, Brisbane, Queensland, Australia
| | - Erik Maronde
- Department of Anatomy, Goethe University Frankfurt, Frankfurt, Germany
| | - Warrick Inder
- Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
- Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
| | - Oliver Rawashdeh
- School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
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6
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Petrenko V, Philippe J, Dibner C. Time zones of pancreatic islet metabolism. Diabetes Obes Metab 2018; 20 Suppl 2:116-126. [PMID: 30230177 DOI: 10.1111/dom.13383] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 05/04/2018] [Accepted: 05/23/2018] [Indexed: 12/28/2022]
Abstract
Most living beings possess an intrinsic system of circadian oscillators, allowing anticipation of the Earth's rotation around its own axis. The mammalian circadian timing system orchestrates nearly all aspects of physiology and behaviour. Together with systemic signals originating from the central clock that resides in the hypothalamic suprachiasmatic nucleus, peripheral oscillators orchestrate tissue-specific fluctuations in gene transcription and translation, and posttranslational modifications, driving overt rhythms in physiology and behaviour. There is accumulating evidence of a reciprocal connection between the circadian oscillator and most aspects of physiology and metabolism, in particular as the circadian system plays a critical role in orchestrating body glucose homeostasis. Recent reports imply that circadian clocks operative in the endocrine pancreas regulate insulin secretion, and that islet clock perturbation in rodents leads to the development of overt type 2 diabetes. While whole islet clocks have been extensively studied during the last years, the heterogeneity of islet cell oscillators and the interplay between α- and β-cellular clocks for orchestrating glucagon and insulin secretion have only recently gained attention. Here, we review recent findings on the molecular makeup of the circadian clocks operative in pancreatic islet cells in rodents and in humans, and focus on the physiologically relevant synchronizers that are resetting these time-keepers. Moreover, the implication of islet clock functional outputs in the temporal coordination of metabolism in health and disease will be highlighted.
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Affiliation(s)
- Volodymyr Petrenko
- Division of Endocrinology, Diabetes, Hypertension and Nutrition, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Institute of Genetics and Genomics in Geneva (iGE3), Geneva, Switzerland
| | - Jacques Philippe
- Division of Endocrinology, Diabetes, Hypertension and Nutrition, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland
- Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Institute of Genetics and Genomics in Geneva (iGE3), Geneva, Switzerland
| | - Charna Dibner
- Division of Endocrinology, Diabetes, Hypertension and Nutrition, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Institute of Genetics and Genomics in Geneva (iGE3), Geneva, Switzerland
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Jiang W, Zhao S, Shen J, Guo L, Sun Y, Zhu Y, Ma Z, Zhang X, Hu Y, Xiao W, Li K, Li S, Zhou L, Huang L, Lu Z, Feng Y, Xiao J, Zhang EE, Yang L, Wan R. The MiR-135b-BMAL1-YY1 loop disturbs pancreatic clockwork to promote tumourigenesis and chemoresistance. Cell Death Dis 2018; 9:149. [PMID: 29396463 PMCID: PMC5833454 DOI: 10.1038/s41419-017-0233-y] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2017] [Revised: 12/03/2017] [Accepted: 12/12/2017] [Indexed: 02/07/2023]
Abstract
Circadian disruption has been implicated in tumour development, but the underlying mechanism remains unclear. Here, we show that the molecular clockwork within malignant human pancreatic epithelium is disrupted and that this disruption is mediated by miR-135b-induced BMAL1 repression. miR-135b directly targets the BMAL1 3'-UTR and thereby disturbs the pancreatic oscillator, and the downregulation of miR-135b is essential for the realignment of the cellular clock. Asynchrony between miR-135b and BMAL1 expression impairs the local circadian gating control of tumour suppression and significantly promotes tumourigenesis and resistance to gemcitabine in pancreatic cancer (PC) cells, as demonstrated by bioinformatics analyses of public PC data sets and in vitro and in vivo functional studies. Moreover, we found that YY1 transcriptionally activated miR-135b and formed a 'miR-135b-BMAL1-YY1' loop, which holds significant predictive and prognostic value for patients with PC. Thus, our work has identified a novel signalling loop that mediates pancreatic clock disruption as an important mechanism of PC progression and chemoresistance.
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Affiliation(s)
- Weiliang Jiang
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Senlin Zhao
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jia Shen
- Tumour Initiation and Maintenance Program, NCI-designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
| | - Lihong Guo
- Department of Gastroenterology, Central Hospital of Shengli Oil-field, Dongying, Shandong, China
| | - Yi Sun
- Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yuntian Zhu
- Department of Anesthesiology, Zhejiang Cancer Hospital, Hangzhou, Zhejing, China
| | - Zhixiong Ma
- National Institute of Biological Sciences, Beijing, China
| | - Xin Zhang
- Department of Pathology, Zhejiang Province People's Hospital, Hangzhou, Zhejiang, China
| | - Yangyang Hu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenqin Xiao
- Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Kai Li
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Sisi Li
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Zhou
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Li Huang
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhanjun Lu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yun Feng
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Junhua Xiao
- Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | | | - Lijuan Yang
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Rong Wan
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Petrenko V, Saini C, Giovannoni L, Gobet C, Sage D, Unser M, Heddad Masson M, Gu G, Bosco D, Gachon F, Philippe J, Dibner C. Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression. Genes Dev 2017; 31:383-398. [PMID: 28275001 PMCID: PMC5358758 DOI: 10.1101/gad.290379.116] [Citation(s) in RCA: 80] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 02/02/2017] [Indexed: 01/10/2023]
Abstract
Here, Petrenko et al. present the first integrative analysis of the molecular properties of circadian clocks in α and β pancreatic cells and provide new insights into the complex regulation of islet cell physiology at transcriptional and functional levels. A critical role of circadian oscillators in orchestrating insulin secretion and islet gene transcription has been demonstrated recently. However, these studies focused on whole islets and did not explore the interplay between α-cell and β-cell clocks. We performed a parallel analysis of the molecular properties of α-cell and β-cell oscillators using a mouse model expressing three reporter genes: one labeling α cells, one specific for β cells, and a third monitoring circadian gene expression. Thus, phase entrainment properties, gene expression, and functional outputs of the α-cell and β-cell clockworks could be assessed in vivo and in vitro at the population and single-cell level. These experiments showed that α-cellular and β-cellular clocks are oscillating with distinct phases in vivo and in vitro. Diurnal transcriptome analysis in separated α and β cells revealed that a high number of genes with key roles in islet physiology, including regulators of glucose sensing and hormone secretion, are differentially expressed in these cell types. Moreover, temporal insulin and glucagon secretion exhibited distinct oscillatory profiles both in vivo and in vitro. Altogether, our data indicate that differential entrainment characteristics of circadian α-cell and β-cell clocks are an important feature in the temporal coordination of endocrine function and gene expression.
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Affiliation(s)
- Volodymyr Petrenko
- Endocrinology, Diabetes, Hypertension, and Nutrition, University Hospital of Geneva, CH-1211 Geneva, Switzerland.,Department of Cellular Physiology and Metabolism, Diabetes Center, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.,Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, CH-1211 Geneva, Switzerland
| | - Camille Saini
- Endocrinology, Diabetes, Hypertension, and Nutrition, University Hospital of Geneva, CH-1211 Geneva, Switzerland.,Department of Cellular Physiology and Metabolism, Diabetes Center, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.,Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, CH-1211 Geneva, Switzerland
| | - Laurianne Giovannoni
- Endocrinology, Diabetes, Hypertension, and Nutrition, University Hospital of Geneva, CH-1211 Geneva, Switzerland.,Department of Cellular Physiology and Metabolism, Diabetes Center, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.,Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, CH-1211 Geneva, Switzerland
| | - Cedric Gobet
- Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.,School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
| | - Daniel Sage
- Biomedical Imaging Group, EPFL, CH-1015 Lausanne, Switzerland
| | - Michael Unser
- Biomedical Imaging Group, EPFL, CH-1015 Lausanne, Switzerland
| | - Mounia Heddad Masson
- Endocrinology, Diabetes, Hypertension, and Nutrition, University Hospital of Geneva, CH-1211 Geneva, Switzerland
| | - Guoqiang Gu
- Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37240, USA
| | - Domenico Bosco
- Department of Surgery, Cell Isolation and Transplantation Centre, University Hospital of Geneva, CH-1211 Geneva, Switzerland
| | - Frédéric Gachon
- Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, CH-1015 Lausanne, Switzerland.,School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
| | - Jacques Philippe
- Endocrinology, Diabetes, Hypertension, and Nutrition, University Hospital of Geneva, CH-1211 Geneva, Switzerland
| | - Charna Dibner
- Endocrinology, Diabetes, Hypertension, and Nutrition, University Hospital of Geneva, CH-1211 Geneva, Switzerland.,Department of Cellular Physiology and Metabolism, Diabetes Center, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.,Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, CH-1211 Geneva, Switzerland
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9
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Dibner C, Sadowski SM, Triponez F, Philippe J. The search for preoperative biomarkers for thyroid carcinoma: application of the thyroid circadian clock properties. Biomark Med 2017; 11:285-293. [DOI: 10.2217/bmm-2016-0316] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Accumulating evidence suggests that alterations in the molecular clocks underlying the circadian time-keeping system might be connected to changes in cell cycle, resulting in oncogenic transformation. The hypothalamic–pituitary–thyroid axis is driven by a circadian clock at several levels, with an endocrine feedback loop regulating thyroid-stimulating hormone. Changes in the expression levels of circadian and cell cycle markers may correlate with clinic-pathological characteristics in differentiated follicular thyroid carcinomas. Here we summarize recent advances in exploring complex regulation of the thyroid gland transcriptome and function by the circadian oscillator. We particularly focus on clinical implications of the parallel assessment of the circadian clock, cell-cycle and cell functionality markers in human thyroid tissue, which might help improving preoperative diagnostics of thyroid malignancies.
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Affiliation(s)
- Charna Dibner
- Division of Endocrinology, Diabetes, Hypertension & Nutrition, Department of Medical Specialties, University Hospitals of Geneva, Geneva, Switzerland
- Department of Cell Physiology & Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | | | - Frederic Triponez
- Thoracic & Endocrine Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - Jacques Philippe
- Department of Cell Physiology & Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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Sridhar GR, Sanjana NSN. Sleep, circadian dysrhythmia, obesity and diabetes. World J Diabetes 2016; 7:515-522. [PMID: 27895820 PMCID: PMC5107711 DOI: 10.4239/wjd.v7.i19.515] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 07/12/2016] [Accepted: 08/29/2016] [Indexed: 02/05/2023] Open
Abstract
Synchrony of biological processes with environmental cues developed over millennia to match growth, reproduction and senescence. This entails a complex interplay of genetic, metabolic, chemical, light, hormonal and hedonistic factors across life forms. Sleep is one of the most prominent rhythms where such a match is established. Over the past 100 years or so, it has been possible to disturb the synchrony between sleep-wake cycle and environmental cues. Development of electric lights, shift work and continual accessibility of the internet has disrupted this match. As a result, many non-communicable diseases such as obesity, insulin resistance, type 2 diabetes, coronary artery disease and malignancies have been attributed in part to such disruption. In this presentation a review is made of the origin and evolution of sleep studies, the pathogenic mediators for such asynchrony, clinical evidence and relevance and suggested management options to deal with the disturbances.
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