Morphological change in pancreatic islets, insulin binding and intracellular glucose metabolism in adipocytes of streptozotocin-induced diabetic rats.

Abstract

To examine the diabetogenic mechanism of streptozotocin, a histological study was performed on the pancreatic islets of male Wistar rats 7 days after an intravenous injection of streptozotocin (75 mg/kg). Furthermore, for the investigation into mechanism of insulin resistance in the insulin-dependent diabetic rats, insulin binding, glucose transport, and lipogenesis were studied in the isolated adipocytes of streptozotocin-induced diabetic rats. 1) The rate of weight gain in the control rats and the diabetic rats were 2.2 ± 1.8 g/day and −2.4 ± 2.1 g/day, respectively (p<0.05). The serum insulin levels in the control rats and the diabetic rats were 23.1 ± 10.8 μU/ml and 16.9 ± 10.6 μU/ml respectively (p<0.05). The plasma glucagon levels in the control rats and the diabetic rats were 165.7 ± 124.9 pg/ml. and 151.2 ± 78.2 pg/ml, respectively (p>0.1).2) Microscopic examination of the pancreatic islets of the diabetic rats revealed a severe degranulation and disintegration of B cells. Electron microscopic examination showed a disruption of the intracytoplasmic organelles of B cells with complete degranulation. But the morphology of A cells was normal.3) Maximal specific insulin binding to receptors in the adipocytes of the diabetic rats (2.10 ± 0.30%) showed an increase compared with that of the control rats (1.12 ± 0.21 %) (p<0.05).4) Insulin receptor concentration in the adipocytes of the diabetic rats (2.33 ± 0.43 ng/0.5 × 105 cells) also showed an increase compared with that of control rats (1.03 ± 0.15 ng/0.5 × 105 cells) (p<0.05).5) The average affinities in the adipocytes of the diabetic rats slightly decreased in the low receptor occupancy state compared with that of the control rats.6) Basal and insulin-stimulated glucose transports in adipocytes of the diabetic rats decreased compared with that of the control rats. The maximal glucose transport in the adipocytes of the diabetic rats was 31.7% of the control value (p<0.005).7) Basal and insulin-stimulated lipogenesis in adipocytes of the diabetic rats decreased compared with that of the control rats. The maximal lipogenesis in the adipocytes of the diabetic rats was 38.4% of the control value (p<0.005).It can be concluded that streptozotocin produces a diabetogenic mechanism in Wistar rats by directly injuring the pancreatic B cells and inducing hypoinsulinemia. The insulin resistance in the streptozotocin-induced diabetic rats results from the defects in the intracellular glucose metabolism such as glucose transport and lipogenesis.