MicroRNA-29a is up-regulated in beta-cells by glucose and decreases glucose-stimulated insulin secretion

Abstract

Chronically elevated levels of glucose impair pancreatic beta-cell function while inducing beta-cell proliferation. MicroRNA-29a (miR-29a) levels are increased in several tissues in diabetic animals and mediate decreased insulin-stimulated glucose-transport of adipocytes. The aim was to investigate the impact of glucose on miR-29a levels in INS-1E beta-cells and in human islets of Langerhans and furthermore to evaluate the impact of miR-29a on beta-cell function and proliferation. Increased glucose levels up-regulated miR-29a in beta-cells and human and rat islets of Langerhans. Glucose-stimulated insulin-secretion (GSIS) of INS-1E beta-cells was decreased by forced expression of miR-29a, while depletion of endogenous miR-29a improved GSIS. Over-expression of miR-29a increased INS-1E proliferation. Thus, miR-29a up-regulation is involved in glucose-induced proliferation of beta-cells. Furthermore, as depletion of miR-29a improves beta-cell function, miR-29a is a mediator of glucose-induced beta-cell dysfunction. Glucose-induced up-regulation of miR-29a in beta-cells could be implicated in progression from impaired glucose tolerance to type 2 diabetes.

miRNA-30a-5p-mediated silencing of Beta2/NeuroD expression is an important initial event of glucotoxicity-induced beta cell dysfunction in rodent models

“…miR-29a and miR-29b contributed to the pancreatic beta cell-specific silencing of monocarboxylate transporter 1 [33]. More recently, Bagge et al [34] demonstrated that glucoseinduced upregulation of miR-29a reduced GSIS. He et al [35] Fig.…”

Dietary Regulation of miR-33b and miR-29a in Relationship to Metabolic Biomarkers of Glucose and Lipids in Obese Diabetic Women: A Randomized Clinical Controlled Study

“…However, our study did not show any marked effect of calorie-controlled diet therapy on miR-29a expres- sion. Previous reports have shown the roles of the miR-29 family in the reduction of glucose production, decreased glucose tolerance, and increased insulin synaptic exocytose in human INS-1E β cells (17,35) and in animal models (18). These findings suggest, to some extent, that there is a compensatory role of miR-29a in offsetting high circulating glucose and insulin resistance in obese diabetic humans.…”

“…These findings suggest, to some extent, that there is a compensatory role of miR-29a in offsetting high circulating glucose and insulin resistance in obese diabetic humans. Considering the pathophysiology of T2DM (36), since miR-29a affects the upstream genes of insulin secretion from the β-cells (17,18), we propose that more time is required to assess the probable results of diet therapies on the expression of miR-29a in obese T2DM subjects.…”

“…This family is the key regulator of glucose homeostasis via targeting numerous related genes (13)(14)(15). Several studies have identified the regulatory roles of the miR-29 family (a, b, and c) in glucose metabolism and insulin signaling (15)(16)(17). The over-expression of miR-29a reduces insulin-dependent glucose uptake, reduces cellular and hepatic glucose production (16,18), and suppresses the expression of Syntaxin 1A (Stx1a), a key regulatory gene of insulin synaptic exocytose from the β-cells (16).…”

miR-29a promotes scavenger receptor A expression by targeting QKI (quaking) during monocyte-macrophage differentiation

“…It has also been shown to influence myogenesis in chronic kidney disease (CKD) [16]. Moreover, mir-29a also regulates insulin secretion [17], manifestation of amyotrophic lateral sclerosis (ALS) disease [18], myocardial ischaemiareperfusion injury [19] and immune responses to intracellular bacterial infection [20]. During GM-CSF, IL-6 and Flt-3L mediated monocyte-macrophage differentiation, miR-29a levels are increased [21].…”