Codelivery of a tea extract prevents morbidity and mortality associated with oral vanadate therapy in streptozotocin-induced diabetic rats.

Oral administration of vanadate has a strong hypoglycemic effect but results in toxic side effects like life-threatening diarrhea. Tea is known to have potent antidiarrhea effects. We investigated the potential of suspending the vanadate in a tea decoction to reduce the diarrheatic action of vanadate. A concentrated extract of Lichee black tea was, therefore, added to sodium orthovanadate. Streptozotocin (STZ)-induced diabetic rats were orally gavaged with vanadate suspended in water or in the tea decoction, or with the tea extract alone. Blood glucose levels were assessed daily over 11 weeks with levels greater than 10 mmol/L warranting therapeutic intervention. Both the vanadate/water and vanadate/tea solutions acutely reduced blood glucose. The tea extract alone had no effect. The majority of vanadate/water-treated rats developed diarrhea and mortality rates approached 40%. Vanadate/tea-treated diabetic rats experienced no diarrhea or mortality and liver and kidney analyses (plasma ALT and creatinine, blood urea nitrogen [BUN], and urine-specific gravity) were normal. Animals treated with vanadate/tea retained blood glucose levels less than 10 mmol/L for an average of 24 consecutive days without subsequent treatments. Cataract formation was completely prevented. The mechanism of action of vanadate may have involved beta-cell stimulation because vanadate/tea-treated diabetic rats exhibited normal plasma insulin levels. In summary, because of its long-lasting effects, oral administration, and lack of side effects, vanadate/tea represents a potentially important alternative therapy for an insulin-deficient diabetic state.

[1]  M. Battell,et al.  Vanadium compounds as insulin mimics. , 1999, Metal ions in biological systems.

[2]  R. Dullaart Plasma lipoprotein abnormalities in type 1 (insulin-dependent) diabetes mellitus. , 1995, The Netherlands journal of medicine.

[3]  G. Boden,et al.  Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. , 1996, Metabolism: clinical and experimental.

[4]  Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. , 1998, Biochemistry.

[5]  G. Pierce,et al.  Cataract formation is prevented by administration of verapamil to diabetic rats. , 1989, Endocrinology.

[6]  G. Pierce,et al.  Alterations in Ca2+ binding by and composition of the cardiac sarcolemmal membrane in chronic diabetes. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[7]  A. Bonen,et al.  Muscle glycogen repletion after exercise in trained normal and diabetic rats. , 1984, Journal of applied physiology: respiratory, environmental and exercise physiology.

[8]  K. Thompson Vanadium and diabetes , 1999, BioFactors.

[9]  M. Giordano,et al.  Derangements in Protein Metabolism Induced by Type I Diabetes mellitus , 1997, Mineral and Electrolyte Metabolism.

[10]  S. Tamura,et al.  A novel mechanism for the insulin-like effect of vanadate on glycogen synthase in rat adipocytes. , 1984, The Journal of biological chemistry.

[11]  C. Kahn,et al.  Metabolic effects of vanadyl sulfate in humans with non-insulin-dependent diabetes mellitus: in vivo and in vitro studies. , 2000, Metabolism: clinical and experimental.

[12]  S. Prakash,et al.  Vanadium: a review of its potential role in the fight against diabetes. , 1999, Journal of alternative and complementary medicine.

[13]  J. McNeill,et al.  Effects of bis(maltolato)oxovanadium(IV) are distinct from food restriction in STZ-diabetic rats. , 1997, The American journal of physiology.

[14]  G. Pierce,et al.  Na(+)-H+ exchange in cardiac sarcolemmal vesicles isolated from diabetic rats. , 1990, The American journal of physiology.

[15]  J. Li,et al.  Vanadium salts as insulin substitutes: mechanisms of action, a scientific and therapeutic tool in diabetes mellitus research. , 1996, Critical reviews in biochemistry and molecular biology.

[16]  Andrea Peirce American Pharmaceutical Association practical guide to natural medicines , 1999 .

[17]  J. B. Collip,et al.  THE EFFECTS OF INSULIN ON EXPERIMENTAL HYPERGLYCEMIA IN RABBITS , 1922 .

[18]  G. Swarup,et al.  Inhibition of membrane phosphotyrosyl-protein phosphatase activity by vanadate. , 1982, Biochemical and biophysical research communications.

[19]  Y. Shechter,et al.  Vanadate restores glucose 6-phosphate in diabetic rats: a mechanism to enhance glucose metabolism. , 2000, American journal of physiology. Endocrinology and metabolism.

[20]  J. Domingo,et al.  Oral vanadium administration to streptozotocin-diabetic rats has marked negative side-effects which are independent of the form of vanadium used. , 1991, Toxicology.

[21]  I. Hirsch Intensive treatment of type 1 diabetes. , 1998, The Medical clinics of North America.

[22]  Partial preservation of pancreatic β-cells by vanadian: Evidence for long-term amelioration of diabetes , 1997 .

[23]  J. B. Collip,et al.  THE EFFECT OF PANCREATIC EXTRACT (INSULIN) ON NORMAL RABBITS , 1922 .

[24]  A. Shisheva,et al.  The protein tyrosine phosphatase inhibitor, pervanadate, is a powerful antidiabetic agent in streptozotocin-treated diabetic rats. , 1994, Endocrinology.

[25]  H. McCarthy,et al.  Effects of Chronic Vanadate Administration in the STZ-Induced Diabetic Rat: The Antihyperglycemic Action of Vanadate Is Attributable Entirely to Its Suppression of Feeding , 1994, Diabetes.

[26]  D. Marrero,et al.  Prevention of IDDM: a public health perspective. , 1996, Diabetes research and clinical practice.

[27]  J. McNeill,et al.  Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. , 1985, Science.

[28]  J. Domingo Vanadium and diabetes. What about vanadium toxicity? , 2004, Molecular and Cellular Biochemistry.

[29]  A. Shisheva,et al.  Vanadium salts and the future treatment of diabetes. , 1993, Endeavour.

[30]  W. Muller Diabetes mellitus--long time survival. , 1998, Journal of insurance medicine.

[31]  P. Raskin,et al.  Hypertension in diabetes mellitus. , 1996, Endocrinology and metabolism clinics of North America.

[32]  J. McNeill,et al.  Mechanisms of vanadium action: insulin-mimetic or insulin-enhancing agent? , 2000, Canadian journal of physiology and pharmacology.

[33]  A. Krolewski,et al.  Epidemiology of late diabetic complications. A basis for the development and evaluation of preventive programs. , 1996, Endocrinology and metabolism clinics of North America.

[34]  J. McNeill,et al.  Improvement in cardiac dysfunction in streptozotocin-induced diabetic rats following chronic oral administration of bis(maltolato)oxovanadium(IV). , 1993, Canadian journal of physiology and pharmacology.

[35]  A. Srivastava Anti-diabetic and toxic effects of vanadium compounds , 2000, Molecular and Cellular Biochemistry.