title: Irreversible loss of normal beta-cell regulation by glucose in neonatally streptozotocin diabetic rats.
abstract: 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.
authors.affiliation: Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Cetkovic-Cvrlje
authors.forename: D L
authors.initials: DL
authors.lastname: Eizirik
authors.forename: V
authors.initials: V
authors.lastname: Grill
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D003573:Cytochrome b Group; D007328:Insulin; D012333:RNA, Messenger; D004247:DNA; D005947:Glucose