Effects of low and high dose administration of bis(maltolato)oxovanadium(IV) on <i>fa/fa</i> Zucker rats

Abstract

The fatty Zucker rat, characterized by obesity, hyperinsulinemia, hyperlipidemia, and mild hyperglycemia, has been suggested as an animal model of non-insulin-dependent diabetes mellitus. The present study examined the chronic dose-dependent effect of bis(maltolato)oxovanadium(IV), a potent insulin mimetic, in this animal model of diabetes. Chronic (6 weeks) oral administration of bis(maltolato)oxovanadium(IV) (0.06 mmol.kg-1.day-1, low dose study) was effective in reducing the hyperinsulinemia associated with the fatty Zucker rat model (termination insulin: lean, 82.8 +/- 21.6; fatty, 732 +/- 89.4; fatty treated, 336 +/- 126.6 pmol/L; p < 0.05). Pancreatic perfusion data indicated a significant improvement in insulin secretory function in the fatty rats. The dose dependency of this relationship was observed in the high dose study (0.128 mmol.kg-1.day-1 for 14 weeks), wherein bis(maltolato)oxovanadium(IV) treatment restored plasma insulin levels in the fatty rats to lean levels (termination insulin: lean, 199.2 +/- 17.4; fatty 660.6 +/- 12.6; fatty treated, 153.6 +/- 9.6 pmol/L; p < 0.05) and significantly improved insulin response to a glucose challenge. In addition, bis(maltolato)oxovanadium(IV) treatment (high dose study) ameliorated the age-dependent increase in blood pressure observed in fatty Zucker rats (systolic blood pressure: lean, 127 +/- 10; fatty, 176 +/- 5; fatty treated, 156 +/- 9 mmHg (1 mmHg = 133.3 Pa)). These data indicate that chronic oral administration of bis(maltolato)oxovanadium(IV) in the drinking water was effective in reducing hyperinsulinemia, insulin resistance, glucose intolerance, and hypertension in the fatty Zucker rat.