AMYLIN RELEASE DURING ORAL GLUCOSE-TOLERANCE TEST

y The role of amylin in the beta-cell dysfunction that occurs in patie nts with diabetes mellitus may be important. Amyloid deposits are foun d in the pancreata of subjects with Type 2 diabetes and may contribute to beta-cell death. It is therefore necessary to study amylin secreti on and kinetics to determine whether elevated levels of the peptide ar e due to elevated secretion, reduced clearance or both. The aim of thi s study was to measure amylin dynamics during an oral glucose toleranc e test (OGTT). We also used a mathematical model of beta-cell activity to assess the secretion and kinetics of C-peptide, insulin and amylin in humans during an OGTT. In particular, we were interested in charac terizing the physiological meaning of one of the terms in the model, t he amylin/C-peptide cosecretion factor (sigma). The model has been use d in several pathophysiological conditions and results indicate an ele vated secretion and clearance of amylin in glucose-intolerant states. Amylin clearance has been found to be similar to that of C-peptide, an d much slower than that of insulin. In this study, direct measurements of insulin and amylin secretion in five obese subjects yielded an est imate of the amylin/insulin co-secretion factor of 0.004 with a standa rd deviation (SD) of 0.002. The point estimate of hepatic clearance wa s 80 mi min(-1), which was much lower than that of insulin (507 +/- 94 mi min(-1)). In addition, the estimated hepatic clearance was not sig nificantly different from zero given its high SD of 213 mi min(-1). Th e absence of hepatic extraction of amylin is therefore a plausible hyp othesis, which is also supported by the similarity between amylin and C-peptide clearances. This observation characterizes the physiological meaning of sigma and suggests that this parameter is associated mainl y with p-cell secretion. (C) 1997 by John Wiley & Sons, Ltd.