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 responsiveness 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. Intrastrain transplantation was performed in NMRI and BALB/c mice, and islet grafts were removed and perifused in vitro after 3 and 12 wk. In grafts from both NMRI and BALB/c mice, 16.7 nmol/L glucose induced a biphasic insulin release. When 1 or 5 mmol/L caffeine was included in the perifusion medium, there was a marked potentiation of the glucose-induced insulin release that was at least as responsiveness as fresh untransplanted islets. In the absence of caffeine, 3-wk-old BALB/c grafts reacted less strongly to acetylcholine than did untransplanted islets. The addition of 1 mmol/L caffeine did not enhance the potentiating effect of acetylcholine, whether in untransplanted or transplanted islets. Rather, the interaction between caffeine and acetylcholine appeared negative. We concluded that the glucose-induced insulin secretion exhibits a diminished potentiatory responsiveness to acetylcholine but not to caffeine. The displacement and denervation of transplanted islets is likely to affect either the cholinergic receptors or their mediated influence on intracellular calcium.