Long-term obestatin treatment of mice type 2 diabetes increases insulin sensitivity and improves liver function
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ORIGINAL ARTICLE
Long-term obestatin treatment of mice type 2 diabetes increases insulin sensitivity and improves liver function Paweł A. Kołodziejski1 Ewa Pruszyńska-Oszmałek1 Mathias Z. Strowski2,3 Krzysztof W. Nowak1 ●
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Received: 23 November 2016 / Accepted: 19 April 2017 © Springer Science+Business Media New York 2017
Abstract Purpose Obestatin and ghrelin are peptides encoded by the preproghrelin gene. Obestatin inhibits food intake, in addition to regulation of glucose and lipid metabolism. Here, we test the ability of obestatin at improving metabolic control and liver function in type 2 diabetic animals (type 2 diabetes mellitus). Methods The effects of chronic obestatin treatment of mice with experimentally induced type 2 diabetes mellitus on serum levels of glucose and lipids, and insulin sensitivity are characterized. In addition, alterations of hepatic lipid and glycogen contents are evaluated. Results Obestatin reduced body weight and decreased serum glucose, fructosamine, and β-hydroxybutyrate levels, as well as total and low-density lipoprotein fractions of cholesterol. In addition, obestatin increased high-density lipoproteins cholesterol levels and enhanced insulin sensitivity in mice with type 2 diabetes mellitus. Moreover,
Electronic supplementary material The online version of this article (doi:10.1007/s12020-017-1309-2) contains supplementary material, which is available to authorized users. * Paweł A. Kołodziejski [email protected] [email protected] 1
Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Wolynska Street 35, 60-637 Poznan, Poland
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Department of Hepatology and Gastroenterology & the Interdisciplinary Centre of Metabolism: Endocrinology, Diabetes and Metabolism, Charité-University Medicine Berlin, 13353 Berlin, Germany
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Park-Klinik Weissensee, Internal Medicine – Gastroenterology, Berlin 13086, Germany
obestatin diminished liver mass, hepatic triglycerides and cholesterol contents, while glycogen content was higher in livers of healthy and mice with type 2 diabetes mellitus treated with obestatin. These changes were accompanied by reduction of increased alanine aminotransferase, aspartate aminotransferase, and gamma glutamyl transpeptidase in T2DM mice with type 2 diabetes mellitus. Obestatin increased adiponectin levels and reduced leptin concentration. Obestatin influenced the expression of genes involved in lipid and carbohydrate metabolism by increasing Fabp5 and decreasing G6pc, Pepck, Fgf21 mRNA in the liver. Obestatin increased both, AKT and AMPK phosphorylation, and sirtuin 1 (SIRT1) protein levels as well as mRNA expression in the liver. Conclusion Obestatin improves metabolic abnormalities in type 2 diabetes mellitus, restores hepatic lipid contents and decreases hepatic enzymes. Therefore, obestatin could potentially have a therapeutic relevance in treating of insulin resistance and metabolic dysfunctions in type 2 diabetes mellitus. Keywords Type 2 diabetes mellitus obestatin liver ●
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Abbreviations ACC Acetyl-CoA carbox
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