Irreversible loss of normal beta-cell regulation by glucose in neonatally streptozotocin diabetic rats

Abstract

Summary Animals with NIDDM display abnormal glucose regulation of insulin secretion and biosynthesis. We tested reversibility of abnormal regulation by normoglycaemia using an islet transplantation technique. Inbred non-diabetic and neonatally STZ diabetic rats (n-STZ) were used. Transplantations insufficient to normalize the blood glucose levels (200 islets under kidney capsule) were performed from diabetic to normal (D-N) and from diabetic to diabetic (D-D), as well as from normal to normal (N-N) and from normal to diabetic (N-D) rats. Four weeks after transplantation, graft bearing kidneys were isolated and perfused with Krebs-Henseleit bicarbonate buffer to measure insulin secretion in response to 27.8 mmol/1 glucose and 10 mmol/1 arginine. Four weeks of normoglycaemia failed to restore glucose-induced insulin secretion from n-STZ islets (glucose induced increment: -1.7 + 2. 351-357]Key words Animal models NIDDM, insulin secretion, insulin mRNA, cytochrome b mRNA, islets of Langerhans.The neonatally STZ diabetic rat (n-STZ) is an animal model of NIDDM [review 1, 2]. In n-STZ insulin secretion is markedly abnormal at adult age despite only mild or moderate hyperglycaemia [1,2]. In particular, the insulin reponse to glucose is reduced out of proportion to the decrease in beta-cell mass. Responses to non-metabolised secretagogues, such as L-arginine or phosphodiesterase inhibitors, are however relatively preserved. This pattern of abnormalities bears resem-