ISLET AMYLOID POLYPEPTIDE-LIKE IMMUNOREACTIVITY (AMYLIN) IN RATS TREATED WITH DEXAMETHASONE AND STREPTOZOTOCIN

Islet amyloid polypeptide (IAPP) is a 37 amino acid peptide present in pancreatic β-cells. Pancreatic and circulating IAPP concentrations in rat models of diabetes were measured using a specific radioimmunoassay. Pancreatic IAPP-like immunoreactivity (IAPP-IR) in dexamethasone-treated rats was twice that of the control rats (1571 ± 137 vs 657 ± 176 (S.E.M.; n = 6) pmol/g), and this was reflected by similar changes in the plasma IAPP-IR (272 ± 17 vs 102 ± 10 pmol/l). In streptozotocin-treated rats, pancreatic IAPP-IR (200 + 90 pmol/g) was reduced compared with controls. There was a significant positive correlation between pancreatic and plasma IAPP-IR and insulin, with r values of 0.82 and 0.91 for the plasma and pancreas respectively. Characterization of pancreatic immunoreactivity, using gel chromatography, revealed two peaks of IAPP-IR, one which coeluted with synthetic human amidated IAPP and another peak, presumably a fragment of breakdown product, which eluted later. Chromatography of the plasma IAPP-IR revealed that > 90% of the IAPP-IR eluted in the void volume, although the remaining IR coeluted with the synthetic IAPP standard. These results are not straightforwardly compatible with the suggested role for IAPP as a hormonal, paracrine or autocrine inhibitory regulator of insulin secretion in the maintenance of carbohydrate homeostasis.