GLUCOSE-TRANSPORTER LEVELS IN A MALE SPONTANEOUS NON-INSULIN-DEPENDENT DIABETES-MELLITUS RAT OF THE OTSUKA LONG-EVANS TOKUSHIMA FATTY STRAIN

Otsuka Long-Evans Tokushima Fatty (OLETF) rats are a new strain of spo ntaneous non-insulin-dependent diabetes mellitus (NIDDM) models. To ev aluate the role of glucose transporters (GLUT) in the development of d iabetes in this model, we examined the action of insulin on the transl ocation of GLUT4 and GLUT1 in isolated adipocytes, and the GLUT4 prote in levels in muscles. Long-Evans Tokushima Otsuka (LETO) rats were use d as a control strain. In adipocytes, the GLUT4 protein levels in OLET F rats at 30 weeks of age (diabetic stage) were considerably lower tha n those in LETO rats at the same age. At a pre-diabetic stage (7 weeks ), there were no significant differences in GLUT4 protein levels in ad ipocytes between LETO and OLETF rats. However, the degree of GLUT4 tra nslocation in OLETF rats was lower than that in LETO rats at 7 weeks o f age. There were no differences in GLUT1 levels in adipocytes between the two strains. In muscles: the decrease in GLUT4 protein was observ ed in OLETF rats at 30 weeks of age. Whether such a difference is unde r the influence of hyperglycemia was also examined using rats rendered diabetic by 70% pancreatectomy. OLETF rats aged 7 weeks were subjecte d to partial pancreatectomy (Pr) and sham pancreatectomy (sham). At 4 weeks after surgery, GLUT4 protein levels in adipose tissues and skele tal muscles were determined. GLUT4 decrease was observed for both tiss ues of hyperglycemic Pr rats compared with euglycemic sham. Moreover, we examined the direct effect of glucose on GLUT4 protein using primar y cultured adipocytes of OLETF rats at 5 weeks of age. After 7-day cul ture with normal (5.6 mmol/l) or high (25 mmol/l) concentrations of gl ucose, the GLUT4 protein levels in adipocytes decreased at 25 mmol/l g lucose compared with 5.6 mmol/l glucose. These findings suggest an ear ly defect in the insulin resistance of OLETF rats probably reflects im paired GLUT4 translocation. The GLUT4 decrease, which occurs later in the process appears to be a consequence, rather than a cause of diabet es in OLETF rats. (C) 1997 Elsevier Science Ireland Ltd.