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In vivo effects of insulin and bis(maltolato)oxovanadium (IV) on PKB activity in the skeletal muscle and liver of diabetic rats

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Abstract

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 PKBα activity more than 10‐fold and PKBβ activity more than 3‐fold in both animal models. Despite the development of insulin resistance, insulin‐induced activation of PKBα was not impaired in the STZ‐diabetic rats up to 9 weeks of diabetes, excluding a role for PKBα in the development of insulin resistance in type 1 diabetes. Insulin-induced PKBα 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 PKBa 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 PKBα and PKBβ 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 PKBα (but not PKBβ) was markedly altered in both tissues; (iii) changes in PKBα activity were tissue specific; (iv) the glucoregulatory effects of BMOV were independent of PKB activity.

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Authors and Affiliations

  1. Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada

    Lucy Marzban & John H. McNeill

  2. Kinetek Pharmaceuticals Inc., Vancouver, BC, Canada

    Sanjay Bhanot

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  1. Lucy Marzban
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Marzban, L., Bhanot, S. & McNeill, J.H. In vivo effects of insulin and bis(maltolato)oxovanadium (IV) on PKB activity in the skeletal muscle and liver of diabetic rats. Mol Cell Biochem 223, 147–157 (2001). https://doi.org/10.1023/A:1017943200785

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