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Wfs1 mutation makes mice sensitive to insulin-like effect of acute valproic acid and resistant to streptozocin

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Abstract

Valproic acid (VLP) is a widely used anticonvulsant and mood-stabilizing drug that relieves the endoplasmic reticulum (ER) stress response, a pathogenetic process related to diabetes. The aim of the present study was to evaluate whether acute valproic acid is able to interfere with glucose intolerance in two different diabetes models: The first model was a Wfs1 mutant mouse with an elevated ER stress response and the second model a streptozocin-induced diabetic mouse. VLP (300 mg/kg, i.p.) was administered to Wfs1 knockout (KO) mice and glucose tolerance test was performed 15 min later. VLP did not have an effect on the course of the glucose tolerance test in wild-type mice, while it did normalize the glucose intolerance in Wfs1 knockout mice. Acute valproic acid also lowered the blood glucose levels in streptozocin-treated mice and potentiated the effect of insulin in these mice. Thus, acute valproic acid is effective in lowering blood glucose levels possibly by potentiating insulin action in both Wfs1 KO mice and in streptozocin-induced type 1 diabetic mice.

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Acknowledgments

This study was supported by grants GARFS 0062J and GARFS 8414 (AT), GARFS 7479 (SK), GARBK 7856 (US), and SF0180148s08 (TARFS0416, EV) from the Estonian Science Foundation and PARFA 08902 (VM) from the University of Tartu.

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Authors and Affiliations

  1. Department of Physiology, University of Tartu, 19 Ravila Street, 50411, Tartu, Estonia

    Anton Terasmaa, Julia Oflijan, Marite Punapart, Vallo Matto, Anne Must, Sulev Kõks & Eero Vasar

  2. Department of Biochemistry, University of Tartu, 19 Ravila Street, 50411, Tartu, Estonia

    Ursel Soomets, Mats Hansen & Kersti Ehrlich

  3. Centre of Excellence for Translational Medicine, 19 Ravila Street, 50411, Tartu, Estonia

    Anton Terasmaa, Ursel Soomets, Julia Oflijan, Marite Punapart, Mats Hansen, Vallo Matto, Kersti Ehrlich, Anne Must, Sulev Kõks & Eero Vasar

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  1. Anton Terasmaa
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Correspondence to Anton Terasmaa.

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Terasmaa, A., Soomets, U., Oflijan, J. et al. Wfs1 mutation makes mice sensitive to insulin-like effect of acute valproic acid and resistant to streptozocin. J Physiol Biochem 67, 381–390 (2011). https://doi.org/10.1007/s13105-011-0088-0

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  • DOI: https://doi.org/10.1007/s13105-011-0088-0

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