Failure to establish islet amyloid polypeptide (amylin) as a circulating beta cell inhibiting hormone in man

Abstract

The presence of islet amyloid polypeptide in amyloid within pancreatic islet cells in Type 2 (non-insulin-dependent) diabetes, and its reported inhibition of glucose uptake by skeletal muscle in vitro, has prompted speculation concerning its role in the pathogenesis of diabetes. We investigated the effect of infused synthetic amidated human islet amyloid polypeptide (mol. wt. 3904, confirmed by mass spectroscopy) on intravenous glucose tolerance. Seven healthy, non-obese volunteers (age±SD, 27±4 years) were infused over 50 min with normal (0.9%) saline or islet amyloid polypeptide at 50 pmol·kg⁻¹·min⁻¹. After 20 min, a bolus of 0.5 g/kg glucose was given within 1 min and blood sampling continued for up to 60 min. Circulating concentrations of islet amyloid polypeptide reached at steady state were 1130±90 pmol/l. The calculated half-life was 11.8±0.9 min, metabolic clearance rate 5.7±0.6 ml·kg⁻¹·min⁻¹ and apparent distribution space therefore 94±12 ml/kg. However, islet amyloid polypeptide was found to have no effect on the peak value reached, or the total area under the curve for plasma glucose, insulin or glucagon following intravenous glucose. This study suggests circulating islet amyloid polypeptide may not be an important influence on intravenous glucose tolerance in man.