Long-term correction of STZ-diabetic rats after short-term Lp. VOSO4 treatment: Persistence of insulin secreting capacities assessed by isolated pancreas studies

摘要

We have previously shown that 3 week oral VOSO4 treatment of streptozotocin (STZ, 60 mg/kg)-mduced diabetic rats was able to correct diabetes for 13 weeks after treatment withdrawal. In the present study, we investigated whether a short-term (8 days) i.p. VOSO4 treatment was similarly able to reverse the diabetic state. Insulin secretory capacities were assessed at distance of treatment using the isolated pancreas preparation. Seven treatment-groups were performed: high dose VOSO4 -treated diabetics (HVD, 1.3 mM/kg/8 days), food-restricted diabetics (FRD, food adjusted to HVD levels), low dose VOSO4-treated diabetes (LVD, 0.06 mM/kg/day), insulin-treated diabetics (ID, dose adjusted to normalize glycaemia) and VOSO4 (0.06 mM/kg/day) + insulin (dose adjusted to normalize glycaemia in the presence of vanadium)-treated diabetics (IVD), in addition to the corresponding untreated non-diabetic controls (C) and diabetics (D). Our results indicate that long-term cor-rection of diabetes (a) can be obtained after an 8 day treatment using i.p. VOSO4 in diabetic animals retaining some degree of pancreatic function, (b) is not obtained with insulin treatment or food restriction although the association of VOSO4 and insulin was found beneficial, (c) can be prolonged in some individuals for at least 4 months, i.e. in conditions such that tis-sue vanadium concentrations had returned to values close to pre-treatment levels, (d) is associated with improved and in some cases normalized insulin secretion from isolated pancreas. The protective or corrective role of VOSO4 on diabetes-:related pancreatic alterations, as well as the potential of the VOSO4-insulin association should be further studied in view of the possible use of vanadium derivatives in the treatment of diabetes.