INHIBITORY EFFECT OF AMYLIN (ISLET AMYLOID POLYPEPTIDE) ON INSULIN-RESPONSE TO NON-GLUCOSE STIMULI - STUDY IN PERFUSED RAT PANCREAS

Amylin, also called islet amyloid polypeptide (IAPP), can inhibit the glucose-induced insulin secretion in perfused rat pancreas at 75 pmol/ l, a concentration comparable to that found in the effluent of this ex perimental model. To further explore the influence of amylin on insuli n release, we investigated the effect of synthetic rat amylin (75 pmol /l) on insulin response to non-glucose secretagogues. These agents sti mulate B-c ell secretion via different mechanisms, such as a dihydropy ridine derivative (BAY K 8644, 10 mmol/l) which activates Ca-2+-channe ls, a sulfonylurea (tolbutamide, 0.2 mmol/l) which blocks ATP-dependen t K+-channels, KCL (11 mmol/l) which depolarizes B cells and the 26-33 fragment of cholecystokinin (8-CCK, 1 nmol/l) which increases phospho lipid turnover. The study was performed in perfudsed rat pancreas. Amy lin significantly inhibited insulin response to BAY K 8644 (65 %), KCI (60 %) and 8-CCK (80 %) as well as the early phase of tolbutamide-ind uced insulin output(70 %). Thus, amylin can inhibit insulin release in duced by secretagogues that interact at different levels of B-cell sti mulus-secretion coupling. This inhibition may be due to a multifarious influence of amylin on the B-cell secretory mechanism and/or a distur bing effect on a distal, crucial step in the insulin-releasing mechani sm, e.g. by affecting exocytosis of the secretory granule or by inhibi ting an essential metabolic pathway within the B cell.