Dec 12, 2007

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

Luan ShuKathrin Maedler


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
Western Blotting

Related Feeds

American Diabetes Association Journals

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


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