Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2016; 7(19): 534-546
Published online Nov 15, 2016. doi: 10.4239/wjd.v7.i19.534
Linagliptin alleviates fatty liver disease 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
Svetlana V Michurina, Irina Ju Ishenko, Sergey A Archipov, Laboratory of Functional Morphology, Scientific Institute of Clinical and Experimental Lymphology, 630060 Novosibirsk, Russia
Vadim V Klimontov, Natalia E Myakina, Marina A Cherepanova, Laboratory of Endocrinology, Scientific Institute of Clinical and Experimental Lymphology, 630060 Novosibirsk, Russia
Eugenii L Zavjalov, Galina V Koncevaya, SPF-vivarium, Institute of Cytology and Genetics of Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
Vladimir I Konenkov, Laboratory of Clinical Immunogenetics, Scientific Institute of Clinical and Experimental Lymphology, 630060 Novosibirsk, Russia
Author contributions: Michurina SV, Klimontov VV and Konenkov VI designed the research; Ishenko IJ, Myakina NE and Zavjalov EL conducted the experiments; Ishenko IJ, Archipov SA and Cherepanova MA performed the morphological investigations; Michurina SV, Ishenko IJ and Klimontov VV analyzed the data; Zavjalov EL and Koncevaya GV performed the biochemical investigations; Michurina SV, Ishenko IJ and Klimontov VV wrote the paper.
Supported by Grants from the Russian Ministry of Education and Science, Nos. 14.621.21.0010, RFMEFI62114X0010 and 14.619.21.0005, RFMEFI61914X0005.
Institutional review board statement: The protocol was approved by the Ethics Committee of Institute of Clinical and Experimental Lymphology (Protocol Number 1/2, April 1, 2014) and Inter-Institutional Animal Ethics Committee based on the Institute of Cytology and Genetics SB RAS (Permission Number: 21, April 1, 2014).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Russian National Center of Genetic Resources of Laboratory Animals based on the SPF Vivarium of the Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia (Permission Number: 246, April 8, 2014).
Conflict-of-interest statement: Klimontov VV received speaker honoraria from Boehringer Ingelheim. All other authors declare no conflicts of interests.
Data sharing statement: Statistical codes and the dataset are available from the corresponding author: klimontov@mail.ru.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Vadim V Klimontov, MD, PhD, Professor of Medicine, Deputy Director for Science, Head of the Laboratory of Endocrinology, Laboratory of Clinical Immunogenetics, Scientific Institute of Clinical and Experimental Lymphology, Timakov Street 2, 630060 Novosibirsk, Russia. klimontov@mail.ru
Telephone: +7-913-9568299 Fax: +7-383-3335122
Received: June 25, 2016
Peer-review started: June 28, 2016
First decision: August 5, 2016
Revised: August 18, 2016
Accepted: September 7, 2016
Article in press: September 9, 2016
Published online: November 15, 2016
Processing time: 137 Days and 14.6 Hours
Core Tip

Core tip: Dipeptidyl peptidase 4 (DPP4) inhibitors are a relatively new class of hypoglycemic agents with multiple pleiotropic effects. In this study, we demonstrated that the DPP4 inhibitor linagliptin alleviates liver steatosis and diminishes structural changes in hepatic non-parenchymal compartments in db/db diabetic mice. The mechanism of the beneficial effect of linagliptin seems to be glucose-independent as no obvious hypoglycemic activity of the agent was observed in this model. The results of the study provide further evidence that linagliptin could be a promising agent for the treatment of non-alcoholic fatty liver disease in subjects with type 2 diabetes.