TCF7L2 Regulates Late Events in Insulin Secretion From Pancreatic Islet -Cells

associated with reduced insulin secretion and an increased risk of type 2 diabetes. However, the mechanisms by which TCF7L2 affect insulin secretion are still unclear. We define the effects of TCF7L2 expression level on mature -cell function and suggest a potential mechanism for its actions. RESEARCH DESIGN AND METHODS—TCF7L2 expression in rodent islets and -cell lines was altered using RNAi or adenoviral transduction. -Cell gene profiles were measured by quantitative real-time PCR and the effects on intracellular signal-ing and exocytosis by live cell imaging, electron microscopy, and patch clamp electrophysiology. RESULTS—Reducing TCF7L2 expression levels by RNAi de-creased glucose- but not KCl-induced insulin secretion. The glucose-induced increments in both ATP/ADP ratio and cytosolic free Ca2 concentration ([Ca2]i) were increased compared wit