Effects of peptide HI on basal and stimulated insulin and glucagon secretion in the mouse

Abstract

Peptide HI (PHI) is a peptide with 27 amino acids that is structurally similar to VIP (vasoactive intestinal peptide). Since PHI, like VIP, has been demonstrated to occur in intrapancreatic neurons, and since VIP earlier was shown to stimulate insulin and glucagon secretion in the mouse, we investigated whether also PHI affects islet hormone secretion in this species. PHI was thereby injected intravenously at dose levels between 0.5 and 8.0 nmol/kg. It was found that PHI did not affect basal levels of insulin of glucagon. However, a slight hyperglycemia was observed after injection of PHI at dose levels above 4.0 nmol/kg. When injected together with glucose (2.8 nmol/kg), PHI (1.0 and 4.0 nmol/kg) potentiated the insulin response by approximately 35% (P < 0.05) and 50% (P < 0.01), respectively. In contrast, the insulin response to the cholinergic agonist carbachol (0.16 μmol/kg) or the β 2-adrenoceptor agonist terbutaline (3.6 μmol/kg) was not affected by PHI. The glucagon response to carbachol was potentiated by PHI (1.0 and 4.0 nmol/kg) by approximately 40% (P < 0.05) and 55% (P < 0.01), respectively, whereas the terbutaline-induced increase in plasma glucagon levels was not affected by PHI. In summary, PHI potentiates glucose-induced insulin secretion and carbachol-induced glucagon secretion in the mouse. Since similar effects earlier have been demonstrated for VIP, it is concluded that PHI in this species exerts VIP-like effects.