LONG-TERM ANTIDIABETIC ACTIVITY OF VANADYL AFTER TREATMENT WITHDRAWAL- RESTORATION OF INSULIN-SECRETION

In its vanadate (V5+) or vanadyl (V4+) forms, vanadium has been demons trated to possess antidiabetic activity. Oral treatment of streptozoto cin (STZ)-diabetic animals with either form is associated with correct ion of hyperglycemia, and prevention of diabetes-induced complications , although weight gain is unaffected. Vanadium treatment of non-diabet ic animals lowers plasma insulin levels by reducing insulin demand, as these animals remain normoglycemic. These results suggest that vanadi um has in vivo insulin-mimetic or insulin-enhancing effects, in agreem ent with several in vitro observations. Chronic treatment with vanadiu m has also been shown to result in sustained antidiabetic effects in S TZ-diabetic animals long after treatment has ceased. Thus, at 13 weeks after withdrawal from treatment, corrected animals had normalized glu cose and weight gain, and improved basal insulin levels. In addition, near-normal glucose tolerance was found despite an insignificant insul in response. Since vanadium accumulates in several tissue sites (e.g. bone, kidney) when pharmacological doses are administered, it is possi ble that stored vanadium may be important in maintaining near-normal g lucose tolerance at least in the short-term following withdrawal from treatment. Recently, following withdrawal of vanadyl treatment up to 3 0 weeks, diabetic animals which had remained normoglycemic and had nor malized glucose tolerance showed improvements in plasma insulin levels both in the basal state and in response to oral glucose, as compared to those which had reverted to hyperglycemia. The observed significant improvements in insulin capacity over the long-term (>3 months) sugge sts that a restored and/or preserved insulin secretion may be essentia l for maintained reversal of the diabetic state over a prolonged perio d after treatment is withdrawn.