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/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.
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Abbreviations
- NIDDM:
-
non-insulin-dependent diabetes mellitus
- STZ:
-
streptozotocin
- O.D.:
-
optical density
- IRI:
-
immunoreactive insulin
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Inoue, K., Cetkovic-Cvrlje, M., Eizirik, D.L. et al. Irreversible loss of normal beta-cell regulation by glucose in neonatally streptozotocin diabetic rats. Diabetologia 37, 351–357 (1994). https://doi.org/10.1007/BF00408470
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DOI: https://doi.org/10.1007/BF00408470