In vivo and in vitro suppression by leptin of glucose-stimulated insulin hypersecretion in high glucose-fed rats

Objectives: Chronic feeding to rats of high glycaemic index (GI) diets resu lts in the hypersecretion of insulin in response to an i.v. glucose load. T he first aim of this study was to see if this exaggerated insulin response was accompanied by a hypersensitivity to glucose stimulation in isolated is lets in vitro. The second aim was to see if the adipocyte factor, leptin, w as able to alter insulin secretion in this model both in vivo and in vitro. Design and methods: Rats were fed for 6 weeks either a high GI diet in whic h the carbohydrate component was mostly glucose (GLUC diet) or a low GI die t containing mostly amylose (AMOSE diet). Rats then underwent an i.v. gluco se tolerance test (ivGTT) (1 g/kg) with and without a prior infusion of lep tin (133 mu g/kg per h). Islets were then isolated from these rats and basa l and glucose-stimulated insulin secretion (GSIS) measured in both the abse nce and presence (100 ng/ml) of leptin. Results and conclusions: Peak insulin response during the ivGTT was 3-fold greater in GLUC rats (P < 0.001). Leptin had no effect on AMOSE rat insulin response but lowered the GLUC rat response to AMOSE rat levels. In vitro, basal insulin secretion was 4-fold greater in GLUC rats (P< 0.05). At 20 mm ol/l glucose, there was no further increase in insulin secretion in GLUC ra ts but a 2-fold increase in AMOSE rats. Leptin had no effect on basal insul in secretion or GSIS in AMOSE rats but reduced basal insulin secretion and GSIS in GLUC rats. These results show insulin hypersecretion in high GI-fed rats may be reduced by leptin.