Abstract
The bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), VO(dmpp)2, has shown anti-diabetic effects by in vitro studies in Wistar (W) rat adipocytes and in vivo in obese Zucker rats. The aim of this work is to confirm the therapeutic properties of VO(dmpp)2 in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. An in vivo study was carried out, treating W and GK rats during 21days with a daily dose of VO(dmpp)2 (44μmol/kg). It was shown that VO(dmpp)2 doesn't affect the normal increase of body weight of both W and GK rats, after 8days of treatment ameliorates glycemia in GK rats (8.4±0.3 vs 10.1±0.2mM in GK control, P<0.001) but doesn't interfere with glucose levels in W rats and, after 21days of treatment, improves the glucose intolerant profile of GK rats (13.1±0.5 vs 20.6±0.7mM/min in GK control, P<0.001), despite no increase of plasma insulin levels during glucose tolerance test. Additionally, it was demonstrated that VO(dmpp)2 significantly enhances [3-3H]-glucose uptake by W and GK rat adipocytes (non-toxic concentration of 100μM: respectively 193±20 and 254±21%, P<0.001, relative to the basal value) showing an efficacy similar to insulin 1.72nM and better than the same concentration of BMOV (P<0.01). Western blotting revealed that in W and GK rats VO(dmpp)2 significantly promotes IRS2 (P<0.05) and p-AKT expression (P<0.001 and P<0.05, respectively, relative to the respective controls) and in GK animals reduces the increase of PTP1β expression (P<0.001, relative to GK control).
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