Effect of Linagliptin on the Ratio of Apoptosis Regulators in the Model of Non-Alcoholic Fatty Liver Disease in db/db Mice

Bull Exp Biol Med. 2019 Jun;167(2):210-214. doi: 10.1007/s10517-019-04493-1. Epub 2019 Jun 24.

Abstract

We studied the effects of dipeptidyl peptidase 4 (DPP4) inhibitor linagliptin on the expression of apoptosis regulator proteins Bcl-2 and Bad in the liver of db/db mice with genetically determined obesity and type 2 diabetes mellitus. The mice received daily linagliptin or saline (placebo) by gavage from week 10 to week 18 of life. In the liver of non-treated mice, the area positively stained for Bad was greater than the area of Bcl-2 expression, which created the conditions for apoptosis activation in liver at this age. Administration of linagliptin decreased Bad stained area and increased Bcl-2 stained area in the liver cells. At the same time, Bad stained area remained larger in treated mice than the area of Bcl-2 expression area, which attested to partial normalization of pro- and antiapoptotic protein balance.

Keywords: apoptosis; db/db mice; linagliptin; liver; type 2 diabetes mellitus.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Diabetes Mellitus, Type 2
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Linagliptin / therapeutic use*
  • Liver
  • Male
  • Mice
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Obesity / drug therapy
  • Obesity / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • bcl-Associated Death Protein / metabolism

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-Associated Death Protein
  • Linagliptin