Inactivation Of Protein Tyrosine Phosphatase (PTPASE)-Linked Insulin Receptor Mediated the Hypoglycemic Effect of Vanadyl Sulfate

Junaidi Khotib, NIDN0022107001 and Grace Syahril and Dian Hasianami and Sumarno and Didik Hasmono (2008) Inactivation Of Protein Tyrosine Phosphatase (PTPASE)-Linked Insulin Receptor Mediated the Hypoglycemic Effect of Vanadyl Sulfate. In: The 8th Asian Conference on Clinical Pharmacy: Toward Harmonisation of education and Practice of Asian Clinical. Faculty of Pharmacy Airlangga University, Surabaya.

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Background: Recent clinical studies have well established that the treatment of antidiabetic medicine to the patient caused several problems including physical and mental burden,insulin tolerance and desensitization, antidiabetic agent resistance and severe side effects. To overcome these important problems and find the replacements for the conventional and unspecific antidiabetic-targeted medicines, we attempted to develop a new pharmacological agent for diabetic treatment using a specific target of protein signaling-dependent insulin activity. The selective activation of the certain enzyme-linked insulin receptor produced a specific effect with corroborative its biological potency and limitative several side effects. The specific compound that could be selective bounded with key enzyme of insulinreceptor was explored in this research. Objective:The study was design to investigate the relationship of selective and specificity inactivation of protein tyrosine phosphatase by vanadyl sulfate with their hypoglycemic effects. Then, we were explore the molecular mechanisms of vanadyl sulfate mediated a decreasing of blood glucose level through specific binding with certain enzymes in the insulin signaling pathway. The combination of molecular and histopathological approaches was applied to measure several parameters that was indicated the involved protein/enzyme sin the insulin signaling pathway. Method;The diabetic model was elicited by twice intraperitoneal injection of streptozotocin 100 mg/kg followed with 50 mg/kg. Diabetes mellitus occurred on day 26 after streptozotocin injection and it was represented with the increasing of blood glucose concentration from 155,6 ± 40,2 mg/dl to 251,1 ± 48,9 mg/dl. The various dose of a selective protein tyrosine phosphatase (PTPase) inhibitor, vanadyl sulphate, were administeredonce a day for 7 concecutives days. Result:The in vivo studies shown that orally repeated treatment with vanadyl sulfateat 30-200 mg/kg, produced a significant decrease of blood glucose level in the streptozotocininduced diabetic mice (30 mg/kg, p = 0,002; 50 mg/kg,p=0,001;100 mg/kg,p=0,017;150 mg/kg,p=0,001; 200 mg/kg, p=0,001), whereas the lower doses have no effect(1mg/kg, p=0,128;10 mg/kg,p=0,223). Using histopathological approaches, we found that repeated treatment with vanadyl sulfate was drastically attenuated the destruction of beta-pancreas cells, atrophy of both skeletal musde and adipose cells, and accumulation of fatty add in liver. Although, the vanadyl sulfate has a potential effect as hypoglycemic agent, the mechanism underlying an insulin-mimicry effect was unclear until now. Currently, our group have succeed to develop the adipose cell culture, that were highly expressed the functional insulin receptors. These works could be conferred an expectation to study the mechanisms under lying insulin-mimicry effect of vanadyl sulfateas a prospective antidiabetic agent. Conclusion: Finally, we condude that vanadyl sulfate have a potency as an antidiabetic with speafic enzyme target. We, therefore, propose here that administration of vanadyl sulfatemay pave the way for thenew strategy for the controlof diabetic state.

Item Type: Book Section
Uncontrolled Keywords: antidiabetic, diabetic-animal model, insulin signaling pathway, steptozotocin, vanadylsulfate
Subjects: R Medicine
R Medicine > RS Pharmacy and materia medica
Divisions: 05. Fakultas Farmasi
Junaidi Khotib, NIDN0022107001UNSPECIFIED
Depositing User: Mr M. Fuad Sofyan
Date Deposited: 15 Aug 2019 01:40
Last Modified: 23 Aug 2019 06:49
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