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| 1 | Linagliptin alleviates fatty liver disease in diabetic db/db mice显示文摘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(BKS.Cg-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 independent to changes in the plasma glucose levels. CONCLUSION The DPP4 inhibitor linagliptin alleviates liver steatosis and structural changes in the hepatic microvasculature and lymphatic roots in a model of NAFLD in diabetic db/db mice. | 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 | 2016 | World Journal of Diabetes2016，7，19： | 2 |
| 2 | Characteristics of selenium migration in soil-plant system of East Meshchera and Transbaikalia显示文摘 | Vadim E Larisa J | 2010 | Journal of Geochemical Exploration2010，107，： | 1 |
| 3 | Optimal control of cooling process in continuous casting of steel u- sing a visualization based multi-criteria approach 显示文摘 | ALEXANDER V GEROGE K VADIM E | 2005 | Ap- plied Mathematical Modelling2005，29，7： | 1 |
| 4 | Towards a framework for agent - enabled semantic web service composition 显示文摘 | VADIM E NATALYA K | 2004 | Interna- tional Journal of Web Service Research2004，1，3： | 1 |
| 5 | Laser diodes emitting up to 25 W at 808 nm显示文摘 | V V Bezotosnyi Vadim Yu Bondarev Oleg N Krokhin G T Mikaelyan V A Oleshchenko Valerii F Pevtsov Yurii M Popov E A Cheshev | 2009 | Quantum Electronics2009，，3： | 1 |
| 6 | Ultrasound Densitometric analysis of carotid plaque composition显示文摘 | Roger E Marjorie F | 1996 | Stroke1996，27，12： | 1 |
| 7 | On multi-input chattering free second order sliding mode control显示文摘 | Bartolini G Ferrara A Usai E Vadim I Utkin | 2000 | IEEE Trans Auto Contr2000，45，9： | 1 |
| 8 | Invariant NKT cells promote CD8+ cytotoxic T cell responses by inducing CD70 expression on dendritic cells显示文摘 | Vadim Y Taraban Sonya Martin Kathrine E | 2008 | J Immunol2008，180，： | 1 |
| 9 | NMR chemical shifts of common laboratory solvents as trace impurities 显示文摘 | HUGO E G VADIM K ABRAHAM N | 1997 | J Org Chem1997，62，21： | 1 |
| 10 | Normal modes for predicting protein motions: a comprehensive database assessment and associated Web tool显示文摘 | Vadim A Ursula L Nathaniel E | 2005 | Protein Sci2005，14，： | 1 |
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