Role of insulin in glucose-stimulated insulin secretion in beta cells.
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 beta 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 beta 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, beta 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 beta cell insulin receptors), or in the absence of constitutively secreted insulin (anti-insulin treatment), beta 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.
Goren
H Joseph
HJ
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada. goren@ucalgary.ca
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism / Q000502:physiology*; D006019:Glycolysis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D010085:Oxidative Phosphorylation; D015398:Signal Transduction
D007328:Insulin; D005947:Glucose