In vivo effects of vanadium in diabetic rats are independent of changes in PI-3 kinase activity in skeletal muscle.
The PI-3 kinase signalling pathway is an important pathway in mediating the glucoregulatory effects of insulin and skeletal muscle (SKM) is the major tissue involved in glucose utilization. In diabetes this pathway is impaired, either due to lack of insulin as in Type I diabetes, or due to insulin resistance as in Type 2 diabetes. Bis(maltolato)-oxovanadium IV (BMOV), an insulin mimetic/enhancing agent, produces a marked glucose lowering effect in models of both types of diabetes. Some in vitro studies have shown that phosphatidylinositol 3 kinase (PI-3 kinase) activity is enhanced by vanadium. In the present study we looked at changes in PI-3 kinase expression and activity in SKM from STZ-diabetic and fa/fa Zucker rats treated with BMOV for 3 weeks. Although BMOV treatment completely normalized glucose levels in STZ-diabetic rats, no effect was observed on basal or insulin-stimulated PI-3 kinase activity. In fatty Zucker rats, activation of PI-3 kinase activity after insulin injection was impaired as compared to age matched lean controls, but BMOV again did not affect the activity. These results suggest that although PI-3 kinase is an important signalling factor in glucose utilization, vanadium treatment does not reduce hyperglycemia through activation of SKM PI-3 kinase in vivo.
Mohammad
A
A
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Bhanot
S
S
McNeill
J H
JH
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011753:Pyrones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D015398:Signal Transduction / Q000502:physiology; D014638:Vanadates / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011753:Pyrones; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D019869:Phosphatidylinositol 3-Kinases