Low doses of vanadate and Trigonella synergistically regulate Na+/K + -ATPase activity and GLUT4 translocation in alloxan-diabetic rats.
Oral administration of vanadate to diabetic animals have been shown to stabilize the glucose homeostasis and restore altered metabolic pathways. However, vanadate exerts these effects at relatively high doses with several toxic effects. Low doses of vanadate are relatively safe but unable to elicit any antidiabetic effects. The present study explored the prospect of using low doses of vanadate with Trigonella foenum graecum, seed powder (TSP), another antidiabetic agent, and to evaluate their antidiabetic effect in diabetic rats. Alloxan diabetic rats were treated with insulin, vanadate, TSP and low doses of vanadate with TSP for three weeks. The effect of these antidiabetic compounds was examined on general physiological parameters, Na(+)/K(+) ATPase activity, membrane lipid peroxidation and membrane fluidity in liver, kidney and heart tissues. Expression of glucose transporter (GLUT4) protein was also examined by immunoblotting method in experimental rat heart after three weeks of diabetes induction. Diabetic rats showed high blood glucose levels. Activity of Na(+)/K(+) ATPase decreased in diabetic liver and heart. However, kidney showed a significant increase in Na(+)/K(+) ATPase activity. Diabetic rats exhibited an increased level of lipid peroxidation and decreased membrane fluidity. GLUT4 distribution was also significantly lowered in heart of alloxan diabetic rats. Treatment of diabetic rats with insulin, TSP, vanadate and a combined therapy of lower dose of vanadate with TSP revived normoglycemia and restored the altered level of Na(+)/K(+) ATPase, lipid peroxidation and membrane fluidity and also induced the redistribution of GLUT4 transporter. TSP treatment alone is partially effective in restoring the above diabetes-induced alterations. Combined therapy of vanadate and TSP was the most effective in normalization of altered membrane linked functions and GLUT4 distribution without any harmful side effect.
Siddiqui
Mohammad Rizwan
MR
Hormone and Drug Research Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
Moorthy
Krishnan
K
Taha
Asia
A
Hussain
Mohd Ejaz
ME
Baquer
Najma Zaheer
NZ
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004341:Drug Evaluation; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D008517:Phytotherapy; D028321:Plant Preparations / Q000008:administration & dosage / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D029910:Trigonella; D014638:Vanadates / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D008563:Membrane Lipids; D028321:Plant Preparations; C495694:Slc2a4 protein, rat; D014638:Vanadates; D000254:Sodium-Potassium-Exchanging ATPase