Distinct glucose lowering and beta cell protective effects of vanadium andfood restriction in streptozotocin-diabetes

Vanadium is an oral insulin-mimetic agent that diminishes hyperglycemia, im proves beta-cell insulin store and secretory function, and can reverse the diabetic state chronically after withdrawal from treatment. As food restric tion has been reported to enhance insulin sensitivity and reduce insulin de mand, we assessed the contribution of a reduced food intake to the glucose lowering and beta-cell protective effects of vanadium. Streptozotocin (STZ) -diabetic rats were untreated (D) or administered vanadyl sulfate in the dr inking water (DT) at one week prior to and for 5 weeks following the admini stration of STZ. An additional group was pair-fed (DP) with an equal amount of food as that consumed by the DT group. Shortly after the induction of d iabetes, hyperglycemic D rats demonstrated a significant rise in plasma ins ulin to levels that initially exceeded that of the controls. This was follo wed by a steady reduction over several weeks, suggesting a gradual depletio n of functional beta-cells. Both vanadium treatment and pair-feeding abolis hed the insulin hypersecretory response following STZ administration. Gluco se lowering was enhanced in DT animals when administered higher concentrati ons of vanadium, despite no further reduction in food intake, and all DT an imals (10/10) were normoglycemic by 5 weeks. Mean pancreatic insulin conten t in DT rats was improved fourfold and was associated with a greater number of granulated bets-cells. Conversely, food restriction only modestly impro ved glycemia and the pancreatic insulin store and, unlike DT, DP rats remai ned highly glucose-intolerant. At 5 weeks of diabetes, fed circulating gluc ose and insulin levels were strongly correlated (P=0.0002) in the D and DP groups, supporting the notion that glucose lowering with food restriction i s dependent on improved plasma insulin levels. A separate correlation was o bserved in DT animals within a lower range of plasma insulin, suggesting th at vanadium, unlike food restriction, reduced plasma glucose by enhancing i nsulin sensitivity Thus, vanadium preserves beta-cells in STZ-diabetes at l east partially by abolishing the insulin hypersecretory response and the ev entual exhaustion of residual insulin stores following a moderate dose of S TZ. This property of vanadium would appear to be useful in the treatment of prediabetic and newly diagnosed insulin-dependent diabetes mellitus.