Rima Hayanty Ritonga and Budi Suprapti and Junaidi Khotib (2015) The Influence of Sodium Orthovanadate on P85 and GSK-3 Expressions to the Blood Glucose Regulation of Type 2 Diabetic Mice (Mus Muculus) Model. International Journal of Pharmacy and Pharmaceutical Sciences, 7 (1). pp. 115-119. ISSN 0975-1491

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Abstract

Objective: The present study was designed to investigate the influence of sodium orthovanadate on the P85 (Regulatory Subunit of PI3-Kinase) and GSK-3 (Glycogen Synthase Kinase 3) expressions in skeletal muscle tissue to the decreasing of blood glucose levels of alloxan-induced diabetic mice. Methods: Mice were divided into 5 groups i. e. (1) naive group, (2) diabetic group and (3-5) orthovanadate-treated diabetic groups at the dose of 16, 32 and 64 mg/kg BW respectively. Diabetic mice model was induced by intraperitoneal administration of alloxan monohydrate at the dose of 200 mg/kgBW. Diabetic state was occurred on day 3 after alloxan injection and then started the treatment of sodium orthovanadate for 7 days. The muscular tissue was harvested on day 10 after treatment and was stained using routine histology staining, haematoxylin-eosin for morphological qualitative analysis and immunohistochemical approaches to observe the expressions of P85 and GSK-3 in skeletal muscle. Results: Diabetes condition was shown by the increasing of fasting blood glucose levels from 59.1 ± 11.2 mg/dL to 310.6 ± 107.2 mg/dL on day 3. Administration of sodium orthovanadate at the dose of 16, 32 and 64 mg/kg BW reduced the fasting blood glucose levels after 7 days treatment (p < 0.001) at diabetic mice significantly. The results of histology staining showed that sodium orthovanadate improved a necrosis in skeletal muscle cells alloxan-induced diabetic mice. On immunohistochemical approaches, sodium orthovanadate might decreased the P85 expressions and increased the GSK-3 expressions in skeletal muscle cells alloxan-induced diabetic mice (p < 0.001). Conclusion: This study reveals that the administration of sodium orthovanadate on diabetic mice led to the attenuation of the PTPase activity. The inhibition cause a decreasing the expression of P85 and increasing of GSK-3 that cause the decreasing of blood glucose levels and an improvement of insulin target cells in the muscle cells.

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