ISLET AMYLOID POLYPEPTIDE AMIDE CAUSES PERIPHERAL INSULIN RESISTANCE INVIVO IN DOGS

Islet amyloid polypeptide is a 37 amino acid hormone-like peptide which is the major protein component of islet amyloid deposits commonly found in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Recent studies indicate that a physiologically active form of this peptide appears to be carboxyamidated and secreted from the insulin-producing beta cell. In order to clarify the possible in vivo actions of islet amyloid polypeptide, we have studied the effects of synthesized islet amyloid polypeptide-amide on peripheral glucose utilization by performing hyperinsulinaemic euglycaemic glucose clamp studies on dogs. Exogenously administered islet amyloid polypeptide-amide (an infusion from 1.0 to 100 μg·kg-1·h-1, over 2 h) inhibited the insulin-stimulated glucose disposal rate in a dose dependent manner. Twenty-five μg·kg-1·h-1 of islet amyloid polypeptide-amide infused via a peripheral vein significantly lowered the glucose disposal rate by 20% (from 17.4±1.7 to 14.4±1.7 mg·kg-1·min-1, n = 5, p<0.01). These findings suggest that islet amyloid polypeptide-amide causes peripheral insulin resistance in vivo. © 1990 Springer-Verlag.