Amylin release during oral glucose tolerance test.
The role of amylin in the beta-cell dysfunction that occurs in patients with diabetes mellitus may be important. Amyloid deposits are found in the pancreata of subjects with Type 2 diabetes and may contribute to beta-cell death. It is therefore necessary to study amylin secretion and kinetics to determine whether elevated levels of the peptide are due to elevated secretion, reduced clearance or both. The aim of this study was to measure amylin dynamics during an oral glucose tolerance 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 characterizing the physiological meaning of one of the terms in the model, the amylin/C-peptide co-secretion factor (sigma). The model has been used in several pathophysiological conditions and results indicate an elevated secretion and clearance of amylin in glucose-intolerant states. Amylin clearance has been found to be similar to that of C-peptide, and much slower than that of insulin. In this study, direct measurements of insulin and amylin secretion in five obese subjects yielded an estimate of the amylin/insulin co-secretion factor of 0.004 with a standard deviation (SD) of 0.002. The point estimate of hepatic clearance was 80 ml min(-1), which was much lower than that of insulin (507 +/- 94 ml min[-1]). In addition, the estimated hepatic clearance was not significantly different from zero given its high SD of 213 ml min(-1). The absence of hepatic extraction of amylin is therefore a plausible hypothesis, 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 mainly with beta-cell secretion.