Abstract
Diabetes is a metabolic disease characterized by hyperglycemia. Over 90% of patients with diabetes have type 2 diabetes. Pancreatic β-cells are endocrine cells that produce and secrete insulin, an essential endocrine hormone that regulates blood glucose levels. Deficits in β-cell function and mass play key roles in the onset and progression of type 2 diabetes. Apoptosis has been considered as the main contributor of β-cell dysfunction and decrease in β-cell mass for a long time. However, recent studies suggest that β-cell failure occurs mainly due to increased β-cell dedifferentiation rather than limited β-cell proliferation or increased β-cell death. In this review, we summarize the current advances in the understanding of the pancreatic β-cell dedifferentiation process including potential mechanisms. A better understanding of β-cell dedifferentiation process will help to identify novel therapeutic targets to prevent and/or reverse β-cell loss in type 2 diabetes.
Highlights
We aim to summarize current knowledge about the underlying mechanisms involved in β-cell dedifferentiation
Other studies have shown that β-cell dedifferentiation or trans-differentiation occurs in animals and humans with Type 2 DM (T2DM) [12,16,20,21]. β-cell dedifferentiation is mostly mediated by downregulation of β-cell-specific enriched genes such as transcription factors, insulin, and genes related to glucose metabolism and the upregulation of forbidden genes in normal β-cells and enriched genes in islet progenitor cells and other mature islet cell types [19,22]
The pathology of islets in patients with T2DM is characterized by infiltration of immune cells, proinflammatory cytokines, chemokines, apoptosis, and amyloid deposits that induce fibrosis and, at least in part, pancreatic β-cell dysfunction [38,39]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Β-cell dedifferentiation is mostly mediated by downregulation of β-cell-specific enriched genes such as transcription factors, insulin, and genes related to glucose metabolism and the upregulation of forbidden genes in normal β-cells and enriched genes in islet progenitor cells and other mature islet cell types [19,22]. The activation of these genes lead to loss of β-cell characteristics, such as insulin synthesis and secretion, thereby resulting in β-cell dysfunction [23]. Β-cell dedifferentiation may be a detrimental factor for β-cell dysfunction in the early or middle stages of the development of diabetes
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