Synergistic interaction of magnesium and vanadate on glucose metabolism in diabetic rats

The effect of vanadate (V) alone, magnesium (Mg) alone, and the combination of Mg plus V (MgV) on insulin-mediated glucose disposal and glucose tolerance was investigated in normal and streptozotocin-induced diabetic rats. MgV, magnesium sulfate (MgSO₄) and sodium metavanadate (NaV) were added to the drinking water of normal or diabetic rats (~300 g) for 3 weeks. After 3 weeks of V treatment (both MgV and NAY), diabetic rats demonstrated a normal meal tolerance test without any increase in the plasma insulin response. Rats also received a euglycemic insulin clamp (12 mU/kg · min for 120 minutes) with 3-³H-glucose infusion to quantify total body glucose disposal, glycolysis (³H₂O production), and glycogen synthesis (total body glucose disposal minus glycolysis). Total glucose disposal was decreased in diabetic versus control rats (29 ± 2 v 35 ± 2 mg/kg · min, P < .01) and returned to levels greater than the nondiabetic control values after MgV (41 ± 2, P < .01). Supersensitivity to insulin was not observed in diabetic rats treated with NaV (34 ± 1). Glycogen synthesis was increased by both MgV and NaV treatment (23 ± 21, P < .01 and 18 ± 1, P < .05 v 14 ± 2 mg/kg · min) in diabetic rats. A small increase in glycolysis was observed in MgSO₄ and MgV rats (18 ± 1 and 18 ± 1 v 16 ± 1, P < .05). NaY alone had no effect on glycolysis. Thus, Mg has a synergistic effect with V to increase muscle glycogen synthesis in diabetic rats. In normal rats, neither MgSO₄ nor NaY had any effect on glucose utilization. However, MgV increased glucose disposal to rates that were significantly higher than the rate in untreated control rats (P < .05). Based on these results, MgV is superior to either V alone or Mg alone in improving insulin sensitivity and glycogen synthesis in diabetic rats.