FUNCTIONAL-ASPECTS OF MOUSE ISLETS TRANSPLANTED TO THE KIDNEY

To test whether the transplantation of pancreatic islets affects their basic functions, collagenase-isolated mouse islets were inserted unde r the left renal capsule of recipient animals. After various periods o f time, grafts were removed from the kidney and examined for insulin c ontent and secretory dynamics in a perifusion system. During syngeneic (C57BL/6, BALB/c) or subsyngeneic (NMRI) intrastrain transplantation, the graft insulin content fell drastically during the first week and stayed low for at least 6 weeks; first-phase secretion in general appe ared suppressed. Immunosuppression by cyclosporin A had little effect on (sub)syngeneic grafts but markedly improved the performance of allo transplants. Daily injections of the calcium antagonist, verapamil, en hanced the insulin secretory responses of isolated grafts. whether (su b)syngeneic or allogeneic. In syngeneic and subsyngeneic grafts, the p otentiating effect of acetylcholine on glucose-induced insulin release was markedly diminished, whereas that of caffeine was not. Transplant ed islets also exhibited a subnormal responsiveness to the inhibiting action of noradrenaline. It is concluded that chronic denervation and transplantation of pancreatic islets may cause fundamental changes in the beta-cell responses to physiological regulators of insulin release .