Dec 12, 2007

Transcription factor 7-like 2 regulates beta-cell survival and function in human pancreatic islets

Diabetes
Luan ShuKathrin Maedler

Abstract

Type 2 diabetes is characterized by impaired insulin secretion in response to increased metabolic demand. This defect in beta-cell compensation seems to result from the interplay between environmental factors and genetic predisposition. Genome-wide association studies reveal that common variants in transcription factor 7-like 2 (TCF7L2) are associated with increased risk of type 2 diabetes. The aim of the present study was to establish whether TCF7L2 plays a role in beta-cell function and/or survival. To investigate the effects of TCFL7L2 depletion, isolated islets were exposed to TCF7L2 small interfering RNA (siRNA) versus scrambled siRNA, and beta-cell survival and function were examined. For TCF7L2 overexpression, islets were cultured in glucose concentrations of 5.5-33.3 mmol/l and the cytokine mix interleukin-1 beta/gamma-interferon with or without overexpression of TCF7L2. Subsequently, glucose-stimulated insulin secretion (GSIS), beta-cell apoptosis [by transferase-mediated dUTP nick-end labeling assay and Western blotting for poly(ADP-ribose) polymerase and Caspase-3 cleavage], and beta-cell proliferation (by Ki67 immunostaining) were analyzed. Depleting TCF7L2 by siRNA resulted in a 5.1-fold increase in beta-cell apopt...Continue Reading

Mentioned in this Paper

Metabolic Process, Cellular
Genome-Wide Association Study
Diabetes Mellitus, Non-Insulin-Dependent
TCF Transcription Factors
Structure of Beta Cell of Islet
Apoptosis, Intrinsic Pathway
RNA, Small Interfering
TCF7L2
Caspase-3
Western Blotting

Related Feeds

American Diabetes Association Journals

Discover the latest diabetes research published by the journals from the American Diabetes Association.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis