Is the hypoglycemic action of vanadium compounds related to the suppression of feeding?
Vanadium compounds exhibit effective hypoglycemic activity in both type I and type II diabetes mellitus. However, there was one argument that the hypoglycemic action of vanadium compounds could be attributable to the suppression of feeding-one common toxic aspect of vanadium compounds. To clarify this question, we investigated in this work the effect of a vanadyl complex, BSOV (bis((5-hydroxy-4-oxo-4H-pyran-2-yl)methyl-2-hydroxy-benzoatato) oxovanadium (IV)), on diabetic obese (db/db) mice at a low dose (0.05 mmol/kg/day) when BSOV did not inhibit feeding. The experimental results showed that this dose of BSOV effectively normalized the blood glucose level in diabetic mice without affecting the body weight growth. Western blotting assays on the white adipose tissue of db/db mice further indicated that BSOV treatment significantly improved expression of peroxisome proliferator-activated receptor γ (PPARγ) and activated AMP-activated protein kinase (AMPK). In addition, vanadium treatment caused a significant suppression of phosphorylation of c-Jun N-terminal protein kinase (JNK), which plays a key role in insulin-resistance in type II diabetes. This is the first evidence that the mechanism of insulin enhancement action involves interaction of vanadium compounds with JNK. Overall, the present work indicated that vanadium compounds exhibit antidiabetic effects irrelevant to food intake suppression but by modulating the signal transductions of diabetes and other metabolic disorders.
State Key laboratories of Natural and Biomimetic Drugs and Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China.
Meiling
M
Huang
Yaling
Y
Wu
Na
N
Wang
Ziwei
Z
Wang
Pan
P
Zhao
Xiaoda
X
Yang
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D056831:Coordination Complexes / Q000008:administration & dosage / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D015398:Signal Transduction / Q000187:drug effects; D017968:Vanadium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
D015415:Biomarkers; D056831:Coordination Complexes; D007004:Hypoglycemic Agents; D007328:Insulin; D017968:Vanadium Compounds; C562058:bis((5-hydroxy-4-oxo-4H-pyran-2-yl)methyl 2-hydroxybenzoatato)oxovanadium(IV)