Irreversible loss of normal beta-cell regulation by glucose in neonatally streptozotocin diabetic rats.
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/l glucose and 10 mmol/l arginine. Four weeks of normoglycaemia failed to restore glucose-induced insulin secretion from n-STZ islets (glucose induced increment: -1.7 +/- 2.5 fmol/min in D-N, 1.2 +/- 7.1 fmol/min in D-D). In contrast to normal islets, normoglycaemia reduced insulin mRNA contents (60 +/- 24 in D-N, 496 +/- 119 in D-D; O.D.-arbitrary units). However, arginine-induced secretion was markedly enhanced by diabetic environment in both normal and n-STZ islet grafts. These results indicate that selected aspects of glucose recognition are irreversibly damaged by a long-term diabetic state or, alternatively, by a lasting effect of STZ administration.
Inoue
K
K
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Cetkovic-Cvrlje
M
M
Eizirik
D L
DL
Grill
V
V
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis; D003573:Cytochrome b Group / Q000378:metabolism; D004247:DNA / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D003573:Cytochrome b Group; D007328:Insulin; D012333:RNA, Messenger; D004247:DNA; D005947:Glucose