Chronic insulin exposure with a decrease of insulin receptors results in diminished insulin sensitivity of glucagon gene transcription in pancreatic alpha cells

Abstract

Objectives: Insulin resistance of peripheral tissues like liver, muscle and fat and beta cell dysfunction contribute to the pathogenesis of diabetes mellitus type 2. Considering that insulin inhibits glucagon secretion and gene transcription, hyperglucagonemia and hyperinsulinemia observed in diabetes suggest that insulin resistance also affects the glucagon-producing pancreatic alpha-cells. However, the molecular mechanisms of insulin resistance at the level of the pancreatic islet alpha-cells are unknown. In the present study the effect of chronic insulin treatment on the regulation of glucagon gene transcription in the pancreatic islet alpha cell-line and on different steps of insulin signaling was investigated.