CHRONIC LOW-DOSE ISLET AMYLOID POLYPEPTIDE INFUSION REDUCES FOOD-INTAKE, BUT DOES NOT INFLUENCE GLUCOSE-METABOLISM, IN UNRESTRAINED CONSCIOUS RATS - STUDIES USING A NOVEL AORTIC CATHETERIZATION TECHNIQUE

Islet amyloid polypeptide (IAPP) is a 37-amino acid polypeptide coprod uced with insulin in the beta-cells of the pancreatic islets. The phys iological effects of IAPP have not been established. Although effects on glucose metabolism are seen only at pharmacological doses both in. vitro and in vivo, effects on food intake have been shown at near-phys iological concentrations. The aim of the present study was to investig ate the effects of similar elevations of circulating plasma LAPP level s on glucose metabolism in rats and to evaluate the function of a nove l aortic catheterization technique. In a cross-over design, two sets o f experiments in which conscious unrestrained rats received chronic IA PP infusions at 0 and 2 or 0 and 7 pmol/kg.min were performed. Periphe ral glucose disposal was determined by means of the hyperinsulinemic e uglycemic clamp technique. Chronic elevations of circulating IAPP at c oncentrations that reduced food intake [43.5 +/- 6.2 g (control) vs. 3 5.7 +/- 8.2 g (IAPP; P < 0.01) and 34.0 +/- 2.2 g (control) vs. 28.8 /- 1.4 g (IAPP; P = 0.07) for the 7 and 2 pmol/kg.min experiments, res pectively] had no effect 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 a nd 2 pmol/kg.min experiments, respectively]. Thus, effects on glucose metabolism are unlikely to explain the anorectic effect of IAPP.