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Linagliptin alleviates fatty liver disease in diabetic db/db mice

World Journal of Diabetes 2016年第19期7卷 534-546页

作者： Svetlana V Michurina irina ju ishenko Vadim V Klimontov Sergey A Archipov Natalia E Myakina Marina A Cherepanova Eugenii L Zavjalov Galina V Koncevaya Vladimir I Konenkov Laboratory of Functional Morphology Scientific Institute of Clinical and Experimental Lymphology Laboratory of Endocrinology Scientific Institute of Clinical and Experimental Lymphology SPF-vivarium Institute of Cytology and Genetics of Siberian Branch of Russian Academy of Sciences Laboratory of Clinical Immunogenetics Scientific Institute of Clinical and Experimental Lymphology

AIM To study the effects of linagliptin on the structural signs of non-alcoholic fatty liver disease(NAFLD) in db/db mice. METHODS Male diabetic db /db mice(***-Dock7m+/+Leprdb/J) aged 10 wk received the dipeptidyl peptidase 4(DPP4) inhibitor linagliptin(10 mg/kg) or saline as a placebo once per day by gavage for 8 wk. Intact db/db mice served as controls. Structural changes in the liver were analyzed from light and electron microscopic images of sections from intact, placebo-treated and linagliptin-treated animals. We estimated the changes in hepatocytes, sinusoidal cells, liver microvasculature and lymphatic roots. Hepatic staining for lymphatic vessel endothelial hyaluronan receptor-1(LYVE-1) was assessed by immunohistochemistry. RESULTS In 18-wk-old diabetic mice, liver steatosis(predominantly microvesicular and mediovesicular steatosis) was accompanied by dilation of the roots of the lymphatic system, interlobular blood vessels and bile canaliculi. Compared to saline-treated mice, linagliptin-treated mice exhibited a reduction in the mean numeral densities of hepatocytes with lipid droplets(92.4% ± 1.7% vs 64.9% ± 5.8% per field of view, P = 0.0002) and a lower proportion of hepatocytes with a high density of lipid droplets(20.7% ± 3.6% vs 50.4% ± 3.1%, P = 0.0007). We observed heterogeneous hepatocytes and relatively preserved cell structures in the linagliptin group. Dilation of blood and lymphatic vessels, as well as ultrastructural changes in the hepatocyte endoplasmic reticulum and mitochondria, were alleviated by linagliptin treatment. In intact and placebo-treated mice, immunohistochemical staining for LYVE-1 was observed in the endothelial cells of interlobular lymphatic vessels and on the membranes of some endothelial sinusoidal cells. We observed an enlarged LYVE-1 reaction area in linagliptin-treated mice compared to intact and placebo-treated mice. The improvement in the structural parameters of the liver in linagliptin-treated mice was independe

关键词： Diabetes Obesity Non-alcoholic fatty liver disease Dipeptidyl peptidase 4 Linagliptin

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