INCREASED LEVELS OF CIRCULATING ISLET AMYLOID POLYPEPTIDE IN PATIENTSWITH CHRONIC-RENAL-FAILURE HAVE NO EFFECT ON INSULIN-SECRETION

To elucidate the metabolism of islet amyloid polypeptide (IAPP) with r espect to a possible renal elimination we investigated IAPP levels in 20 lean, nondiabetic patients with renal failure maintained on chronic hemodialysis (HD) and in 20 healthy controls. The basal levels of IAP P were significantly higher in uremic patients than in controls (15.1/-3.2 vs. 3.2+/-0.2 pM, P < 0.001) suggesting renal excretion of IAPP. To investigate the impact of chronically elevated levels of endogenou s IAPP on insulin secretion and insulin sensitivity, a frequently samp led intravenous glucose tolerance test (FSIGT) was performed in a subs et of patients on hemodialysis and in age-matched healthy controls (C) and obese patients with normal (NGT) and with impaired glucose tolera nce (IGT). Insulin sensitivity index (SI) was 8.7+/-1.5 in C (P < 0.05 vs. NGT, P < 0.01 vs. IGT), 5.4+/-0.9 in HD (P < 0.05 vs. IGT). 3.1+/ -1.0 in NGT, and 2.0+/-0.5 in IGT. First phase insulin secretion was i ncreased in patients on HD compared with those of several control grou ps. The results of this study therefore indicate a renal route of meta bolism of IAPP. Increased endogenous circulating IAPP levels over a lo ng period of time do not lead to a decrease in insulin release in pati ents on HD and do not cause the insulin resistance commonly seen in ob esity and diabetes. Increased levels of circulating IAPP therefore are not likely to be a pathogenetic factor in the development of non-insu lin-dependent diabetes mellitus (NIDDM).