INSULIN-SECRETION AND GLUCOSE-TOLERANCE AFTER ISLET TRANSPLANTATION IN RATS WITH NONINSULIN-DEPENDENT DIABETES-INDUCED BY NEONATAL STREPTOZOTOCIN

The present study was designed to identify in a model of noninsulin-de pendent diabetes induced by neonatal streptozotocin (n0-STZ), the long -term consequences of an islet graft upon 1) glucose handling of the r ecipient and, 2) glucose response of the residual beta cells in the re cipient pancreas, We have examined, 4 and 8 mk after islet implantatio n under the kidney capsule of syngeneic diabetic n0-STZ rats, their to lerance to glucose administered in vivo, together with their insulin r elease in response to glucose in vivo (oral glucose tolerance test) as well as in vitro (perfused pancreas), The results in the islet-grafte d n0-STZ rats, were compared to those obtained in nongrafted nondiabet ic rats and nongrafted n0-STZ rats, Our study shows that transplanting a limited number (900) of adult islets under the kidney capsule rever ses to normal, many parameters of the noninsulin-dependent diabetic st ate in the n0-STZ rat model: these include body weight, basal plasma g lucose in both the nonfasted and postabsorptive states, and basal plas ma insulin in the postabsorptive state, Furthermore, tolerance to oral glucose administration was greatly improved in the transplanted rats and it was correlated with restoration of a manifest glucose-induced i nsulin secretion in vivo as evaluated (Delta I) during an oral glucose tolerance test, Our data clearly show that the insulin response to gl ucose from the endogenous pancreas of n0-STZ diabetic rat was not real ly improved by long-term (8 wk) basal normoglycemia. More precisely, w e were able to detect a slight but significant improvement of the earl y phase of insulin release in vitro in response to glucose; however, t he overall insulin response remained 15 times lower than the normal on e with no reapparance of the late phase of insulin release, After cess ation of glucose stimulation in vivo, off-response of insulin, which i s also a landmark of the impaired insulin release by the beta cells of n0-STZ rats, was still detectable in the perfused pancreas of the tra nsplanted n0-STZ rats, Finally, because the reactivity to glucose of t he endogenous residual beta cells was not regained, the insulin releas ed in vivo during the oral glucose test in the graft-bearing n0-STZ ra ts can be attributed mainly to functioning of the grafted islets popul ation. Copyright (C) 1997 Elsevier Science Inc.