Insulin-like effect of vanadyl ion on streptozotocin-induced diabetic rats

Abstract

Recent studies have indicated that the blood glucose level of rats with streptozotocin (STZ)-induced diabetes (type 1) is normalized without an increase in the plasma insulin level by administration of sodium orthovanadate in the drinking water. The mechanism of this insulin-like effect of vanadate is unknown. In this study, we investigated whether vanadyl ion, which is less toxic than vanadate to rats, also has an insulin-like effect in rats with STZ-induced diabetes. When rats with STZ-induced diabetes were given a daily i.p. injection of vanadyl sulphate (9.3 and 4.6 mg vanadium/kg body weight), their blood glucose level decreased from about 22.2 to about 7.2 mmol glucose/l within 2 days and remained low for at least 12 weeks. This treatment did not affect their low plasma insulin level. Quantitative electron spin resonance (ESR) spectrometry showed that most of the vanadium (about 90%) in their tissues was present as a vanadyl form (VO2+). ESR analysis also showed that the vanadyl ion in tissues was bound endogenously with four oxygen ligands from either water or oxyamino acid residues in proteins. Vanadyl sulphate accelerated glucose incorporation into adipocytes of rats, suggesting that the action of vanadyl ion is peripheral. Interestingly, vanadyl sulphate at a high concentration (about 10 mmol/l) was more effective than insulin in enhancing glucose uptake. This study demonstrated that: (1) vanadyl sulphate (+4 oxidation state), like vanadate ion, normalizes the blood glucose levels of rats with STZ-induced diabetes; (2) the action of vanadyl ion is peripheral; and (3) the active form of vanadium for an insulin-like effect may be a vanadyl form, not vanadate.

Vanadate Improves Cardiac Function and Myocardial Energy Metabolism in Diabetic Rat Hearts

“…On the other hand, several studies have demonstrated that the administration of vanadium mimicks the effects of insulin and normalizes the serum concentration of glucose in diabetic rats. 6,7) In contrast to these previous studies, it was insufficient to normalize serum glucose levels in vanadate treatment to STZinduced diabetes mellitus in the present study. Despite the significant increase in serum vanadium, the unsatisfactory glucose lowering effect of vanadium may be due to the different methods for administering vanadium or to the form of its complex.…”

“…1,4,5) Vanadium also exerts insulin-like actions on target tissues and many studies concerning its actions have been reported. [6][7][8][9] In 1985, Heyliger, et al 6) found that vanadium mimicked the metabolic effects of insulin, demonstrating that treatment with vanadium improved cardiac dysfunction in diabetic rat hearts by causing a decrease in blood glucose levels. However, exactly how vanadium regulates intracellular metabolic processes in diabetes mellitus has long been elusive and controversial.…”

Insulin-Mimetic Vanadyl(IV) Complexes as Evaluated by Both Glucose-Uptake and Inhibition of Free Fatty Acids (FFA)-Release in Isolated Rat Adipocytes

“…7) In experimental diabetic animals, both vanadyl and vanadate ions have been found to have an insulin-mimetic effect on glucose metabolism. [8][9][10][11][12][13][14] Interestingly, both compounds have been proposed to partially improve human DM. [15][16][17][18][19][20][21][22][23][24] However, the vanadyl ion is less toxic than the vanadate ion, as judged by the LD 50 values in several animals, 25,26) , and most vanadium in normal rats treated with vanadate exists in the vanadyl form.…”

The vanadium compounds: chemistry, synthesys, insulinomimetic properties

“…На животных с химически индуцированным СД 1 типа ванадий и его соли проявляют гипогликемический, антигиперлипидемический, нефро-, гепато-и кардиопротекторные эффекты, и таким образом минимизируют вторичные последствия СД. Ванадил сульфат при трёхдневном внутрибрюшинном введении в дозах 9,3 и 4,6 мг ванадия/кг снижает уровень гликемии с 22,2 до 7,2 ммоль/л, причем, этот эффект сохраняется в течение, по крайней мере, 12 недель без увеличения уровня эндогенного инсулина [43]. Длительное применение ванадил сульфата у крыс со стрептозотоциновым диабетом приводило к уменьшению концентрации триглицеридов и холестерина в крови [44], нормализации липидного профиля и уменьшению содержания продуктов ПОЛ и неферментативного гликозилирования в желудке и селезенке [45], а также к уменьшению концентрации креатинина и мочевины [46].…”