Vanadate treatment rapidly improves glucose transport and activates 6-phosphofructo-1-kinase in diabetic rat intestine

Abstract

The effect of oral vanadate on intestinal sodium-dependent glucose transport and 6-phosphofructo-1-kinase (EC 2.7.1.11) activity was examined in male Sprague-Dawley rats following a 30-day period of non-treated streptozotocin-induced diabetes. Non-treated diabetic rats were hyperglycaemic and demonstrated increased intestinal sodium-dependent glucose transport and Na,K-ATPase activity compared with controls. These increases were associated with a significant decrease in the total activity and activity ratios (activity at 0.5 mmol/l fructose 6-phosphate at pH 7.0/activity at pH 8.0) of intestinal 6-phosphofructo-1-kinase and decreased levels of fructose 2,6-bisphosphate. Supplementation of drinking water with vanadate (0.5 mg/ml) resulted in a rapid decline in blood glucose levels to a slightly hyperglycaemic level. Jejunal glucose transport and Na,K-ATPase activity were normalized after 48 h of vanadate treatment. In contrast, ileal glucose transport was significantly reduced 12 h following beginning vanadate treatment even though Na,K-ATPase activity did not normalize until 36 h later. Km was significantly decreased in both jejunum and ileum by vanadate treatment indicating an increased affinity of the sodium-dependent intestinal glucose transporter for glucose. 6-phosphofructo-1-kinase total activity and susceptibility to ATP inhibition was completely restored after 12 h of vanadate treatment. This increase was associated with a rise in fructose 2,6-bisphosphate levels. Fasting rats for 12 h had no effect on glucose transport or 6-phosphofructo-1-kinase activity, indicating the anorectic effect of vanadate was not responsible for changes in either parameter. In contrast, cycloheximide prevented both the rise in 6-phosphofructo-1-kinase activity and the rise in fructose 2,6-bisphosphate levels, and the subsequent reduction in glucose transport, indicating a requirement for protein synthesis. The removal of vanadate resulted in an immediate return to pre-treatment blood glucose levels. In contrast, intestinal glucose transport and 6-phosphofructo-1-kinase activity remained at treatment levels up until 72 h, indicating that oral vanadate treatment can have prolonged beneficial effects on intestinal function. In conclusion, the treatment of streptozotocin-induced diabetic rats with oral vanadate results in an activation of 6-phosphofructo-1-kinase coupled with a normalization of intestinal sodium-dependent glucose transport. Vanadate may thus have a beneficial effect on intestinal function and may prove useful as oral adjunctive diabetic therapy.

Effect of Vanadium on the Subset and Proliferation of Peripheral Blood T Cells, and Serum Interleukin-2 Content in Broilers

“…Supplementation of the diet with vanadium could result in a variety of metabolic changes. An important physiological role for vanadium was suggested by the findings that it mimicked the action of insulin [5,6], as a antidiabetic agent [7]. Vanadium also is a potent inhibitor of several phosphohydrolases such as Na + K + -ATPase [8] and Ca 2+ -ATPase [9], an activator of adenyl cyclase [10], and a potent anticarcinogenic agent [11].…”

Effect of dietary vanadium on small intestinal morphology in broilers

“…A number of observations have demonstrated that the biological importance of vanadium [2], such as the insulin-like function [3,4], or the antidiabetic agent [5]. Vanadium also is a potent inhibitor of several phosphohydrolases such as Na + K + -ATPase [6] and Ca…”

Effects of Luminal ATPase Inhibitors on Electrogenic Ion Transport in Rat Distal Colon1

“…Vanadium has been proposed as a therapeutic agent for diabetes [8] and lipid imbalance [9]. However, one must take into account that vanadium species may act as potent inhibitors of several enzymes, including Na ϩ -K ϩ -ATPase [10], K ϩ -ATPases [10] and PTPs [11].…”