Islet amyloid polypeptide (IAPP) is a 37-amino acid polypeptide coproduced with insulin in the β-cells of the pancreatic islets. The physiological effects of IAPP have not been established. Although effects on glucose metabolism are seen only at pharmacological doses both in vitro end in vivo, effects on food intake have been shown at near-physiological concentrations. The aim of the present study was to investigate the effects of similar elevations of circulating plasma IAPP levels on glucose metabolism in rats and to evaluate the function of a novel aortic catheterization technique. In a cross-over design, two sets of experiments in which conscious unrestrained rats received chronic lAPP infusions at 0 and 2 or 0 and 7 pmol/kg · min were performed. Peripheral glucose disposal was determined by means of the hyperinsulinemic euglycemic clamp technique. Chronic elevations of circulating IAPP at concentrations that reduced feed intake [43.5 ± 6.2 g (control) vs. 35.7 ± 8.2 g (IAPP; P < 0.01) and 84.0 ± 2.2 g (control) vs. 28.8 ± 1.4 g (IAPP; P = 0.07) for the 7 and 2 pmol/kg · min experiments, respectively] had no affect on the glucose metabolic rate [GMR; 18.5 ± 0.6 mmol/kg · h (control) vs. 18.7 ± 0.9 mmol/kg · h (IAPP) and 14.4 ± 0.7 mmol/kg · h (control) vs. 15.6 ± 0.7 mmol/kg · h (IAPP) for the 7 and 2 pmol/kg · min experiments, respectively]. Thus, effects on glucose metabolism are unlikely to explain the anorectic effect of IAPP.
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