Distinct glucose lowering and beta cell protective effects of vanadium and food restriction in streptozotocin-diabetes

Abstract

Vanadium is an oral insulin-mimetic agent that diminishes hyperglycemia, improves beta-cell insulin store and secretory function, and can reverse the diabetic state chronically after withdrawal from treatment. As food restriction has been reported to enhance insulin sensitivity and reduce insulin demand, we assessed the contribution of a reduced food intake to the glucose lowering and beta-cell protective effects of vanadium. Streptozotocin (STZ)-diabetic rats were untreated (D) or administered vanadyl sulfate in the drinking water (DT) at one week prior to and for 5 weeks following the administration of STZ. An additional group was pair-fed (DP) with an equal amount of food as that consumed by the DT group. Shortly after the induction of diabetes, hyperglycemic D rats demonstrated a significant rise in plasma insulin to levels that initially exceeded that of the controls. This was followed by a steady reduction over several weeks, suggesting a gradual depletion of functional beta-cells. Both vanadium treatment and pair-feeding abolished the insulin hypersecretory response following STZ administration. Glucose lowering was enhanced in DT animals when administered higher concentrations of vanadium, despite no further reduction in food intake, and all DT animals (10/10) were normoglycemic by 5 weeks. Mean pancreatic insulin content in DT rats was improved fourfold and was associated with a greater number of granulated beta-cells. Conversely, food restriction only modestly improved glycemia and the pancreatic insulin store and, unlike DT, DP rats remained highly glucoseintolerant. At 5 weeks of diabetes, fed circulating glucose and insulin levels were strongly correlated (P=0.0002) in the D and DP groups, supporting the notion that glucose lowering with food restriction is dependent on improved plasma insulin levels. A separate correlation was observed in DT animals within a lower range of plasma insulin, suggesting that vanadium, unlike food restriction, reduced plasma glucose by enhancing insulin sensitivity. Thus, vanadium preserves beta-cells in STZ-diabetes at least partially by abolishing the insulin hypersecretory response and the eventual exhaustion of residual insulin stores following a moderate dose of STZ. This property of vanadium would appear to be useful in the treatment of prediabetic and newly diagnosed insulin-dependent diabetes mellitus.

Biological activity of vanadium compounds

“…1). Their antidiabetic function is not thought to result from the protection of the ß cells of the pancreas [39]. There are, however, findings that deny such suggestions and indicate that vanadium may regenerate the pancreatic β cells in diabetic animals [40].…”

Oxovanadium(IV)–Porphyrin Complex as a Potent Insulin-Mimetic. Treatment of Experimental Type 1 Diabetic Mice by the Complex [meso-Tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadate(IV)(4−)

“…It has been established that vanadium compounds exert an insulin-mimetic action in both in vitro and in vivo systems, including their ability to improve glucose homeostasis and insulin resistance in animal models of DM. [5][6][7] In recent years, several reports have documented vanadium therapyinduced improvements in insulin sensitivity in the liver and muscles of many type 2 diabetic human subjects. [8][9][10] Since the discovery of the orally active insulin-mimetic oxovanadium(IV)-cysteine methyl ester complex for the treatment of streptozotocin (STZ)-induced diabetic rats in 1990, 11 the therapeutic potential of oxovanadium(IV) complexes has been of great interest to us.…”

Inhibition of vagally mediated immune-to-brain signaling by vanadyl sulfate speeds recovery from sickness

“…Some common over-the-counter vitamin supplements contain V (9), and V is claimed to mitigate hyperglycemia (10,11) and build muscle mass (12,13). These insulin and IGF-1 mimetic properties of V may be linked to its ability to inhibit protein tyrosine phosphatases (14) that normally provide negative feedback to protein kinases within the insulin͞IGF-1 signaling cascade (2,(15)(16)(17)(18)(19)(20)(21)(22).…”