We previously reported that bis(maltolato)oxovanadium(IV) (BMOV), an organic vanadium complex, decreased plasma insulin concentrations in nondiabetic rats without affecting plasma glucose levels (McNeill JH, Yuen VG, Hoveyda HR, Orvig C: Bis(maltolato)oxovanadium(IV) is a potent insulin mimic. J Med Chem 35:1489–1491, 1992). In this study, chronic oral BMOV treatment was started in 6-week-old spontaneously hypertensive (SH) rats and their Wistar-Kyoto (WKY) controls, and the effects of the drug on insulin sensitivity, plasma insulin, and blood pressure (BP) were studied. BMOV (0.35–0.45 mmol.kg−1.day−1) caused a sustained reduction in plasma insulin (198 ± 6 vs. untreated 366 ± 13.2 pM, P < 0.0001) and systolic BP (149 ± 3 vs. untreated 184 ± 3 mmHg, P < 0.0001) in SH rats. No changes were seen in WKY rats (plasma insulin: treated 228 ± 4.8 vs. untreated 222.6 ± 3.6 pM, P > 0.05; BP: treated 134 ± 3 vs. untreated 134 ± 5 mmHg, P > 0.05). At 13 weeks of age, euglycemic clamps were performed in fasted, conscious, mobile rats. During low-dose insulin infusions (14 pmol.kg−1 · min−1) with concomitant somatostatin administration, neither hepatic glucose output nor total body glucose uptake differed between the untreated SH and WKY rats. Insulin sensitivity, expressed as steady-state glucose clearance per unit of plasma insulin, was higher in the untreated SH compared with the untreated WKY rats (2.1 ± 0.2 vs. 1.2 ± 0.1 ml.kg−1.h−1.pM−1P < 0.002). BMOV further enhanced insulin sensitivity in SH rats (3.6 ± 0.4, P < 0.002 vs. untreated SH rats). In conclusion, 1) SH rats are hyperinsulinemic but not insulin resistant compared with WKY rats; and 2) BMOV caused concurrent decreases in plasma insulin and BP in SH rats, which suggests that hyperinsulinemia may contribute toward the development of high BP in the SH rat.

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