We determined islet amyloid polypeptide (IAPP) response in plasma to oral and intravenous glucose administration and intravenous insulin injection in nondiabetic subjects. Moreover, we studied the effect of somatostatin analogue SMS 201-995 on glucose-induced IAPP secretion in nondiabetic subjects. Plasma IAPP concentration was determined by radioimmunoassay. Oral administration of 75 g glucose (n = 8) significantly increased plasma IAPP levels from 4.5 ± 0.7 to 14.0 ± 1.7 pM (P < 0.01) 60 min after administration. Intravenous administration of 10 g glucose (n = 7) also caused a significant increase in plasma IAPP from 5.0 ± 0.4 to 11.6 ± 0.9 pM (P < 0.01) 5 min after injection. Plasma IAPP significantly decreased from 5.1 ± 0.4 to 2.9 ± 0.4 pM (P < 0.01) 60 min after intravenous insulin injection (n = 8). Pretreatment with SMS 201-995 completely abolished IAPP and insulin secretion to intravenous glucose injection. A significant correlation was found between plasma IAPP and insulin levels in oral and intravenous glucose administration and between plasma IAPP and C-peptide levels during insulin-induced hypoglycemia. These results suggest that IAPP is cosecreted with insulin in response to a glucose load and secretion of IAPP is inhibited by hypoglycemia and somatostatin. IAPP may serve as a novel pancreatic hormone to control carbohydrate metabolism.

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