Role of Insulin in Glucose-Stimulated Insulin Secretion in Beta Cells

H.   J.   Goren

doi:10.2174/157339905774574301

Abstract

Diabetes is on the increase worldwide and greater than 90% are type 2. There are two features to type 2 diabetes: muscle, fat and liver tissues are insulin resistant and β cells lose the ability to secrete insulin. Prior to developing diabetes, however, insulin resistant individuals lose the first-phase insulin secretion response. Transgenic mice lacking insulin receptors in their β cells have no first-phase response. Primary cultures of mouse islets pre-exposed to anti-insulin do not exhibit a first-phase insulin secretion response. That is, β cells, like muscle, fat, and liver, are an insulin sensitive tissue and in the presence of insulin resistance (type 2 diabetes), in the absence of insulin receptors (transgenic mice lacking β cell insulin receptors), or in the absence of constitutively secreted insulin (anti-insulin treatment), β cells are unable to respond properly to post-prandial glucose. The purpose of this report is to review our understanding of the glucose-stimulus response and of insulin signaling, and to suggest why the latter may be necessary for the former to proceed.

Keywords: insulin signaling, islet glucose oxidation, pyruvate dehydrogenase, glucokinase, anti-insulin inhibition of insulin secretion, b cell communication, constitutively secreted insulin