AMYLIN INSULIN SECRETORY RATIOS IN MORBIDLY OBESE MAN - INVERSE RELATIONSHIP WITH GLUCOSE DISAPPEARANCE RATE/

Amylin/insulin secretory ratios were determined in nine morbidly obese subjects consenting to portal venous catheterization at the time of g astric bypass surgery. By subtracting recirculating insulin and amylin concentrations (arterial values) from portal venous hormone concentra tions, instantaneous amylin/insulin secretory ratios could be determin ed before and after iv glucose administration. Baseline portal venous amylin levels were 32% higher than peripheral concentrations (7.3 +/- 0.8 vs. 5.6 +/- 0.6 pmol/L). Portal venous amylin and insulin concentr ations peak 90 s after the initiation of a 2-min glucose infusion. Whe n instantaneously secreted amylin and insulin were compared at each of the eight time points, a highly significant correlation was observed in seven of the nine subjects. However, large interindividual variatio ns in amylin/insulin secretory ratios were observed, with molar ratios from 0.2-1.6%. The amylin/insulin secretory ratios calculated at the time of surgery varied inversely (r = -0.89; P < 0.001) with glucose d isappearance rates obtained 5-7 months later after 19- to 29-kg weight loss. These data corroborate those obtained from animal studies and i ndicate that amylin and insulin are cosecreted in man. Despite evidenc e for cosecretion of amylin and insulin, the large intersubject variat ion in amylin/insulin secretory ratios and its inverse correlation wit h glucose disappearance rates suggest a constitutional factor that may either play a role in the pathogenesis of carbohydrate intolerance or result from it.