Glucagon-like peptide-1(7-36)-amide confers glucose sensitivity to previously glucose-incompetent beta-cells in diabetic rats: in vivo and in vitro studies

The eVects of glucagon-like peptide-1(7‐36)-amide (GLP-1) on cAMP content and insulin release were studied in islets isolated from diabetic rats (n0-STZ model) which exhibited impaired glucose-induced insulin release. We first examined the possibility of re-activating the insulin response to glucose in the ‚-cells of the diabetic rats using GLP-1 in vitro. In static incubation experiments, GLP-1 amplified cAMP accumulation (by 170%) and glucose-induced insulin release (by 140%) in the diabetic islets to the same extent as in control islets. Using a perifusion procedure, GLP-1 amplified the insulin response to 16·7 mm glucose by diabetic islets and generated a clear biphasic pattern of insulin release. The incremental insulin response to glucose in the presence of GLP-1, although lower than corresponding control values (1·56&0·37 and 4·53&0·60 pg/min per ng islet DNA in diabetic and control islets respectively), became similar to that of control islets exposed to 16·7 mm glucose alone (1·09&0·15 pg/min per ng islet DNA). Since in vitro GLP-1 was found to exert positive eVects on the glucose competence of the residual ‚-cells in the n0-STZ model, we investigated the therapeutic eVect of in vivo GLP-1 administration on glucose tolerance and glucose-induced insulin release by n0-STZ rats. An infusion of GLP-1 (10 ng/min per kg; i.v.) in n0-STZ rats enhanced significantly (P<0·01) basal plasma insulin levels, and, when combined with an i.v. glucose tolerance and insulin secretion test, it was found to improve (P<0·05) glucose tolerance and the insulinogenic index, as compared with the respective values of these parameters before GLP-1 treatment.