DYNAMICS OF GLUCOSE-INDUCED INSULIN RELEASE FROM MOUSE ISLETS TRANSPLANTED UNDER THE KIDNEY CAPSULE

Mouse pancreatic islet grafts under the kidney capsule of syngeneic ho sts were removed and perifused in vitro 1-40 weeks after the transplan tation. In compar ison with fresh isle ts, 12- to 40-week-old grafts e xhibited an attenuated first phase of glucose-stimulated insulin relea se. In grafts 1, 12, 28, or 40 weeks old, but not in fresh islets, the mean secretory rate during the initial 10 min of stimulation was sign ificantly lower than that during the subsequent 15 min. When expressed in relation to insulin content, the insulin output in response to 11 mmol/L glucose was no less from grafts than from fresh islets; in graf ts 12 or 40 weeks old at 16.7 mmol/L glucose, the fractional output ab ove baseline was significantly diminished during the initial 10 min, b ut not subsequently. Immediately on switching from basal to stimulator y glucose concentration, where was a transient drop in insulin secreti on from the grafts, especially after more than 12 weeks of transplanta tion and in response to 16.7, as compared with 11, mmol/L glucose. Whe n glucose was switched back from stimulatory to basal concentration, g rafts also frequently exhibited a transient increase in the insulin se cretory rate. Neither initial drops nor ''off responses'' were seen in untransplanted islets. The modifications of the secretory dynamics in islet grafts suggest that transplantation influences the balance betw een the stimulatory and inhibitory influences of glucose on the beta-c ell's secretory machinery.