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The role of microRNAs in pancreatic islet dysfunction in type 2 diabetes mellitus

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Novel therapeutic targets for diabetes

Identifying the mechanisms underlying the pathogenesis of diabetes should help treat this modern epidemic.

Health

Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with impaired insulin secretion. Obesity and ageing are known to contribute to disease pathogenesis by rendering the pancreas unable to meet the metabolic demands of the associated insulin resistance. However, the underlying mechanism of beta cell loss and dysfunction in T2DM are incompletely understood. Accumulating evidence underscores the role of various microRNAs (miRNAs) in T2DM pathogenesis. miRNAs are a recently discovered class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. As a result, scientists on the EU-funded project 'The role of microRNAs in pancreatic islet dysfunction in type 2 diabetes mellitus' (MIRT2DM) decided to study the role of specific miRNAs in beta cell function, glucose and lipid metabolism, and overall aetiology of T2DM. For this purpose, they used several mouse models of obesity and ageing to identify miRNAs, which are differentially expressed in islets during obesity and ageing. To understand the impact of these miRNAs on physiological pancreatic function, researchers overexpressed them in islets to identify that certain miRNAs stimulated insulin secretion. When beta cells overexpressing these miRNAs were transplanted into mice, improved glucose homeostasis and insulin secretion were observed when these animals switched to a high-fat diet. Collectively, these observations clearly demonstrate the molecular nature of pancreatic cell function regulation. It remains to be determined how expression of these miRNAs gets altered during diabetes and how they induce beta cell function and mass in T2DM. Nonetheless, the concept of miRNAs as therapeutic targets for T2DM is novel and opens up new avenues for future research studies.

Keywords

Type 2 diabetes mellitus, insulin, pancreas, beta cell, miRNAs

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3 December 2021