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

TY - JOUR

T1 - MicroRNA-29a is up-regulated in beta-cells by glucose and decreases glucose-stimulated insulin secretion

AU - Bagge, Annika

AU - Clausen, Trine R

AU - Larsen, Sylvester

AU - Ladefoged, Mette

AU - Rosenstierne, Maiken W

AU - Larsen, Louise

AU - Vang, Ole

AU - Nielsen, Jens Høiriis

AU - Dalgaard, Louise T

N1 - Copyright © 2012 Elsevier Inc. All rights reserved.

PY - 2012/9/21

Y1 - 2012/9/21

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line

KW - Cell Proliferation

KW - Cell Size

KW - Glucose

KW - Glucose Intolerance

KW - Humans

KW - Insulin

KW - Insulin-Secreting Cells

KW - MicroRNAs

KW - Rats

KW - Up-Regulation

U2 - 10.1016/j.bbrc.2012.08.082

DO - 10.1016/j.bbrc.2012.08.082

M3 - Journal article

C2 - 22940552

SN - 0006-291X

VL - 426

SP - 266

EP - 272

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -