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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 Technique¹

Department of Biomedical Sciences, Creighton University School of Medicine (U.A., R.D.R., T.E.A.), Omaha, Nebraska 68178; Research Service (151), Department of Veteran Affairs Medical Center (R.D.R.), Omaha, Nebraska 68105; and Arvid Wretlind Laboratory for Metabolic Research, Department of Surgery, Karolinska Institutet at Huddinge University Hospital (U.A., J.P., J.L., C.A.), S-141 86 Huddinge, Sweden

Address all correspondence and requests for reprints to: Johan Permert, M.D., Ph.D., Department of Surgery, Karolinska Institutet at Huddinge University Hospital, S-141 86 Huddinge, Stockholm, Sweden. E-mail: Johan.Permert{at}karo.ki.se

Islet amyloid polypeptide (IAPP) is a 37-amino acid polypeptide coproduced with insulin in the ß-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 and 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 IAPP 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 food intake [43.5 ± 6.2 g (control) vs. 35.7 ± 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, respectively] 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 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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