THE EFFECT OF GLUCOSE AND GLUCAGON-LIKE PEPTIDE-1 STIMULATION ON INSULIN RELEASE IN THE PERFUSED PANCREAS IN A NON-INSULIN-DEPENDENT DIABETES-MELLITUS ANIMAL-MODEL

This study was designed to investigate the effect of glucogon-like pep tide-1 (GLP-1) on pancreatic P-cell function in normal, Zucker diabeti c fatty (ZDF) rats, a model for non-insulin-dependent diabetes mellitu s (NIDDM or type II diabetes) and their heterozygous siblings. Pancrea s perfusion and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes in insulin release under fasting and hyperglycemic conditions and following stimulation with GLP-1, Animals from the ZDF /Gmi-fa rats (ZDF) were grouped according to age, sex, and phenotype ( obese or lean), and compared with LA lean rats. Glucose stimulation (1 0 mmol/L) in obese rats showed repressed response in insulin release. Glucose plus GLP-1 stimulation caused increased insulin release in all groups. The degree of this response differed between groups: lean > o bese; young > adult; female > male, The LA lean control group was most sensitive, while the ZDF overtly diabetic group had the lowest respon se, In addition, the pulsatile pattern of insulin secretion was suppre ssed in ZDF rats, especially in obese groups. These results support th e hypothesis that GLP-1 can effectively stimulate insulin secretion, I nsulin release was defective in ZDF obese rats and could be partially restored with GLP-1, ZDF lean rats also showed suppression of beta-cel l function and there was a difference in beta-cell function related to sex in ZDF strain. This study documents the efficacy of GLP-1 to stim ulate insulin release and contributes to our understanding of the path ophysiological mechanisms underlying NIDDM. Copyright (C) 1998 by W.B. Saunders Company.