Marked reduction of pancreatic insulin content in male ventromedial hypothalamic-lesioned spontaneously non-insulin-dependent diabetic (Goto-Kakizaki) rats

Abstract

The effects of ventromedial hypothalamic (VMH) lesions were examined in male and female non-obese non-insulin-dependent diabetic (Goto-Kakizaki [GK]) rats with respect to glucose metabolism and pancreatic insulin content. VMH lesions produced hyperphagia and hyperinsulinemia in both male and female GK rats. In male rats, plasma glucose levels of VMH-lesioned GK rats (22.7 ± 3.1 mmol/L) were significantly greater than the levels of sham-operated GK rats (10.6 ± 1.0 mmol/L, P < .001) at 7 weeks after the operation, although there were no differences in these levels between VMH-lesioned and sham-operated groups in Wistar rats. Plasma insulin levels in male VMH-lesioned GK rats tended to be lower at 7 weeks than at 1 week. VMH lesions caused a significant decrease in the pancreatic insulin content of male GK rats (12.0 ± 2.3 nmol/L/g pancreas) compared with male sham-operated rats (15.8 ± 1.4 nmol/L/g pancreas, P < .05) 9 weeks postoperatively. In contrast to the results in male rats, female GK rats showed no differences in plasma glucose levels between VMH-lesioned and sham-operated groups at 7 weeks. Female VMH-lesioned GK rats also showed no difference in plasma insulin levels between 1 week and 7 weeks. The pancreatic insulin level of female VMH-lesioned GK rats was unchanged from that of female sham-operated GK rats. The insulin content was significantly greater in the VMH-lesioned Wistar group than in the sham-operated Wistar group, regardless of sex. These observations suggest that the increased requirement for insulin secretion caused by VMH lesions may lead to B-cell exhaustion, producing, at least in part, marked hyperglycemia in male GK rats. Male VMH-lesioned GK rats might be a good model for obese Japanese patients with the genetic predisposition to non-insulin-dependent diabetes mellitus (NIDDM).