Pancreatic β cell regeneration induced by clinical and preclinical agents

Table 1 Cell types, regeneration mechanisms, and clinical/preclinical agents for pancreatic β cell regeneration

Regeneration mechanisms	Cell types	Clinical/preclinical agents	Ref.
Correction of glucotoxicity and lipotoxicity		All antidiabetic drugs	[16-18]
Suppression of the immune system		Immunomodulation therapies, for instance, activation of the nuclear receptor LRH-1/NR5A2, CD3 mAb, GABA, GLP-1	[21-24]
Inhibition of cell death	Islet β cells	GLP-1, metformin, angiotensin-converting enzyme inhibitors	[25,27,28]
Inhibition of cell dedifferentiation	Islet β cells	Antidiabetic drugs and the diabetes management, such as diet, exercise, or intensive insulin therapy; Other drugs, such as salsalate, renin–angiotensin system inhibitors	[35,36]; [37,38]
Stimulation of cell proliferation	Islet β cells	A large number of growth factors and mitogenic agents, including hepatocyte growth factor, GLP-1, insulin-like growth factors, epidermal growth factors in rodent models; Inhibition of Dyrk1a, SerpinB1, GABA, GLP-1, etc.; Combining of the Dyrk1a inhibitor with the GLP-1 receptor agonist; combined inhibition of Dyrk1a, SMAD and Trithorax pathways	[42]; [48-51]; [52,53]
Promotion of stem cell differentiation	Pluriopotent stem cells	Stepwise induction with cocktails of cytokines and chemicals; GLP-1, ascorbic acid, zinc sulfate, N-acetyl cysteine, etc.	[54-58]; [56,58,65-66]
	Stem cell-derived pancreatic endoderm cells or progenitors	GLP-1	[67]
	Mesenchymal stem cells	Stepwise induction	[63]
	Pancreatic stem or progenitor cells in vivo	GLP-1, dipeptidyl peptidase 4 inhibitor, fasting-mimicking diet, etc.	[79-82]
Induction of cell transdifferentiation and transdetermination	Pancreatic α cells	GABA, artemisins, GLP-1, glucagon receptor mAb, sodium-glucose co-transporter type 2 inhibitor inhibitor, fibroblast growth factor 21, etc.	[87,88,90,91,93,94]
	Pancreatic δ-cells	FoxO1 inhibitor, etc.	[13]
	Pancreatic acinar cells	Cytokine mixture of epidermal growth factor and ciliary neurotrophic factor	[98]
	Enteroendocrine progenitors	FoxO1 inhibition, GLP-1, etc.	[100,104,105]
	Other progenitors and mature cells, including hepatocytes, neuroendocrine cells	Not determined.

GABA: γ-aminobutyric acid; GLP-1: Glucagon-like peptide-1; mAb: Monoclonal antibody.