EFFECTS OF CAFFEINE AND ACETYLCHOLINE ON GLUCOSE-STIMULATED INSULIN RELEASE FROM ISLET TRANSPLANTS IN MICE

In mouse islet grafts under the kidney capsule, the potentiating respo nsiveness to acetylcholine was markedly attenuated after a few weeks, The question arose as to whether transplanted islets show an decreased responsiveness to potentiators in general, The effect of caffeine on glucose-induced insulin secretion was, therefore, examined, Intrastrai n transplantation was performed in NMRI and BALB/c mice, and islet gra fts were removed and perifused in vitro after 3 and 12 wk, In grafts f rom both NMRI and BALB/c mice, 16.7 mmol/L glucose induced a biphasic insulin release, When 1 or 5 mmol/L caffeine was included in the perif usion medium, there was a marked potentiation of the glucose-induced i nsulin release that was at least as responsiveness as fresh untranspla nted islets, In the absence of caffeine, 3-wk-old BALB/c grafts reacte d less strongly to acetylcholine than did untransplanted islets, The a ddition of 1 mmol/L caffeine did not enhance the potentiating effect o f acetylcholine, whether in untransplanted or transplanted islets. Rat her, the interaction between caffeine and acetylcholine appeared negat ive, We concluded that the glucose-induced insulin secretion exhibits a diminished potentiatory responsiveness to acetylcholine but not to c affeine. The displacement and denervation of transplanted islets is li kely to affect either the cholinergic receptors or their mediated infl uence on intracellular calcium. Copyright (C) 1997 Elsevier Science In c.