EFFECTS OF ARGININE ON THE SECRETION OF INSULIN AND ISLET AMYLOID POLYPEPTIDE IN HUMANS

Islet amyloid polypeptide (IAPP) is synthesized in islet B cells and stored in the secretory granules. We examined whether IAPP and insulin are released in parallel in humans. Arginine hydrochloride (5 g) was injected intravenously at three glucose levels in 11 healthy 58-year-old female subjects. In the fasting state (plasma glucose, 4.9 +/- 0.3 mM), serum insulin levels were 62 +/- 8 pM and plasma IAPP levels were 5.9 +/- 0.8 pM (r = 0.74, p < 0.01; insulin/IAPP ratio, 13.4 +/- 3.6). The insulin response to arginine was 426 +/- 84 pM (p < 0.001), whereas the IAPP response was 4.9 +/- 1.8 pM (p < 0.01) (r = 0.93, p < 0.001). At 16.3 +/- 0.5 mM glucose, the insulin response was increased to 1,516 +/- 325 pM (p < 0.001), whereas the IAPP response was increased to 10.4 +/- 2.8 pM (p < 0.01) (r = 0.91, p < 0.001). No further increases were seen at 35.0 +/- 2.0 mM glucose. The ratios of insulin response/IAPP response, which represent the relative secretion of the two peptides, were 169 +/- 31, 158 +/- 17, and 162 +/- 17, at the three glucose levels. Thus, the ratios of the insulin/IAPP responses to arginine were the same regardless of the glucose level, and the insulin and IAPP responses to arginine were highly correlated with each other at all glucose levels. We conclude that the two peptides are cosecreted in strict parallelism after arginine stimulation in humans over a wide range of glucose levels.