In vivo effects of insulin and bis(maltolato)oxovanadium (IV) on PKB activity in the skeletal muscle and liver of diabetic rats.
In this study, the in vivo effects of insulin and chronic treatment with bis(maltolato)oxovanadium (IV) (BMOV) on protein kinase B (PKB) activity were examined in the liver and skeletal muscle from two animal models of diabetes, the STZ-diabetic Wistar rat and the fatty Zucker rat. Animals were treated with BMOV in the drinking water (0.75-1 mg/ml) for 3 (or 8) weeks and sacrificed with or without insulin injection. Insulin (5 U/kg, i.v.) increased PKBalpha activity more than 10-fold and PKBbeta activity more than 3-fold in both animal models. Despite the development of insulin resistance, insulin-induced activation of PKBalpha was not impaired in the STZ-diabetic rats up to 9 weeks of diabetes, excluding a role for PKBalpha in the development of insulin resistance in type 1 diabetes. Insulin-induced PKBalpha activity was markedly reduced in the skeletal muscle of fatty Zucker rats as compared to lean littermates (fatty: 7-fold vs. lean: 14-fold). In contrast, a significant increase in insulin-stimulated PKBalpha activity was observed in the liver of fatty Zucker rats (fatty: 15.7-fold vs. lean: 7.6-fold). Chronic treatment with BMOV normalized plasma glucose levels in STZ-diabetic rats and decreased plasma insulin levels in fatty Zucker rats but did not have any effect on basal or insulin-induced PKBalpha and PKBbeta activities. In conclusion (i) in STZ-diabetic rats PKB activity was normal up to 9 weeks of diabetes; (ii) in fatty Zucker rats insulin-induced activation of PKBalpha (but not PKBbeta) was markedly altered in both tissues; (iii) changes in PKBalpha activity were tissue specific; (iv) the glucoregulatory effects of BMOV were independent of PKB activity.
Marzban
L
L
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; D003920:Diabetes Mellitus / Q000201:enzymology*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology; D005951:Glucose Tolerance Test; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011753:Pyrones / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D014020:Tissue Extracts / Q000737:chemistry; D014638:Vanadates / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D011518:Proto-Oncogene Proteins; D011753:Pyrones; D014020:Tissue Extracts; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt