Recovery of function and mass of endogenous beta-cells in streptozotocin-induced diabetic rats treated with islet transplantation.
Islet transplantation corrects chronic hyperglycemia by augmentation of insulin supply from the graft tissue, but the role of endogenous beta-cells after transplantation is not clear. In the present study, we examined endogenous beta-cell function after glucose homeostasis had been reestablished by islet graft in streptozotocin (STZ)-induced diabetic rats. Fed plasma glucose levels in diabetic rats transplanted with a large number of islets (2500 islets) into the left kidney capsule soon became lower (139.8 +/- 8.2 mg/dl) and close to the level in controls (129.7 +/- 11.3 mg/dl), and IPGTT exhibited a pattern of plasma glucose response almost identical to control. The insulin and DNA contents, islet area, and the distribution of beta-cells that were markedly deteriorated in islets of STZ rats were significantly restored in transplanted rats. The insulin release in response to glucose or alpha-ketoisocaproate was less in STZ rats, while in islets of transplanted rats the secretion recovered to levels similar to controls. On the other hand, arginine-induced insulin release was conversely hyperresponsive in STZ rats, but in transplanted rats, the response was decreased similar to controls. Thus, as the plasma glucose level normalizes, residual beta-cells show a recovery of function that cannot be accounted for by the increase in mass alone.
Hamamoto
Y
Y
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, 54 Syogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. hamamoto@metab.kuhp.kyoto-u.ac.jp
Tsuura
Y
Y
Fujimoto
S
S
Nagata
M
M
Takeda
T
T
Mukai
E
E
Fujita
J
J
Yamada
Y
Y
Seino
Y
Y
D000818:Animals; D017690:Cell Transplantation; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin