We studied the effect of metformin (100 and 200 mg/kg/day, 4 weeks) on the adenylyl cyclasestimulating effects of β-agonists and relaxin in the myocardial membranes and on activities of Akt-kinase, an effector component of insulin signaling, and AMP-activated protein kinase (AMPK), a cellular energy sensor, in the myocardium of rats with type 2 diabetes mellitus induced by high-fat diet and streptozotocin. Metformin normalized the ratio of adenylyl cyclase effects of β1/2- and β3-agonists in the myocardial membranes, that is reduced in DM2, and restored phosphorylation of Akt-kinase by Ser473 and AMPK by Thr172 in the myocardium of diabetic rats. The effect of metformin in a dose of 200 mg/kg/day was more pronounced. Thus, the cardioprotective effect of metformin is due to its ability to restore the adrenergic and insulin regulation in cardiomyocytes and their energy status.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 1, pp. 28-32, January, 2020
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Derkach, K.V., Bondareva, V.M., Kornyushin, O.V. et al. Restoration of β-Adrenergic Signaling and Activity of Akt-Kinase and AMP-Activated Protein Kinase with Metformin in the Myocardium of Diabetic Rats. Bull Exp Biol Med 169, 24–28 (2020). https://doi.org/10.1007/s10517-020-04816-7
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DOI: https://doi.org/10.1007/s10517-020-04816-7