Stimulation of Insulin Release in Isolated Rat Islets by GIP in Physiological Concentrations and Its Relation to Islet Cyclic AMP Content

Several insulinotropic hormones have been shown to increase the level of cyclic AMP in isolated islets. This study was performed to investigate whether gastric inhibitory polypeptide (glucose-dependent insulin-releasing polypeptide) has a similar effect, in particular at concentrations close to the physiological level in blood. Collagenase isolated rat islets were maintained for 24 h in tissue culture (medium 199) and then incubated for 30 min for measurement of insulin release and cyclic AMP content. Glucose-induced (16.7 mmol/l) insulin release was enhanced by gastric inhibitory polypeptide 1-100 ng/ml (0.196-19.6 nmol/l) in a dose-related fashion. The cyclic AMP content was enhanced only by 100 ng/ml. However, when 0.1 mmol/l of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine was present, even 1 ng/ml of gastric inhibitory polypeptide increased both cyclic AMP content and insulin release. Such a concentration of the hormone can be measured in human blood after a meal. In contrast, in freshly isolated islets no effect of the hormone on glucose-induced insulin release or cyclic AMP content could be detected for concentrations ranging from 1 to 100 ng/ml. These findings demonstrate that the hormone sensitivity of isolated islets is markedly enhanced by short-term maintenance in tissue culture. The results suggest that an increase in cyclic AMP is seen in response to gastric inhibitory polypeptide and may be causally related to the insulinotropic effect of the hormone.