EFFECT OF CHRONIC VANADATE ADMINISTRATION IN PARTIALLY DEPANCREATIZEDRATS

The effects of vanadate on B-cell function and replication in rats aft er 90% partial pancreatectomy (Px) were compared with insulin therapy. At the age of 4 weeks, male Wistar rats were subjected to sham operat ion or Px. Vanadate (0.2 mg/ml) was given in drinking water for 3 week s starting at 2 weeks after surgery. Regular insulin (2.4 units/day) w as administered as a continuous subcutaneous infusion through an osmot ic pump. Plasma glucose levels were significantly higher in the Px rat s than in the sham rats from 1 week after surgery. Vanadate lowered pl asma glucose levels to near normal values in the Pr rats as early as 2 days. The effect was sustained throughout the experiment. The hypogly cemic effect of insulin was less than that of vanadate, During an i.p. glucose tolerance test, plasma glucose levels were decreased in the P x rats treated with vanadate or insulin, while plasma insulin levels w ere not affected. The insulin content in the Px rats treated with vana date was significantly (P < 0.01) greater than in the insulin-treated Pr rats, Histological examination showed fibrotic degeneration in the enlarged islets of Pr rats, whereas the normal structure was retained in most islets of the Px rats treated with vanadate and insulin, In ad dition, B-cell areas within the islet were restored to normal levels n ot only in the insulin-treated Pr rats but in the vanadate-treated Px rats. However, both vanadate and insulin failed to stimulate prolifera tive activity of the B-cells. These data suggest that vanadate is a ne w therapeutic option to ameliorate the diabetic state after Px.