Effects of metformin on burn-induced hepatic endoplasmic reticulum stress in male rats

Yaeko Hiyama, Alexandra H. Marshall, Robert Kraft, Nour Qa'aty, Anna Arno, David Herndon, Marc G. Jeschke

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Severe burn injury causes hepatic dysfunction that results in major metabolic derangements including insulin resistance and hyperglycemia and is associated with hepatic endoplasmic reticulum (ER) stress. We have recently shown that insulin reduces ER stress and improves liver function and morphology; however, it is not clear whether these changes are directly insulin mediated or are due to glucose alterations. Metformin is an antidiabetic agent that decreases hyperglycemia by different pathways than insulin; therefore, we asked whether metformin affects postburn ER stress and hepatic metabolism. The aim of the present study is to determine the effects of metformin on postburn hepatic ER stress and metabolic markers. Male rats were randomized to sham, burn injury and burn injury plus metformin and were sacrificed at various time points. Outcomes measured were hepatic damage, function, metabolism and ER stress. Burn-induced decrease in albumin mRNA and increase in alanine transaminase (p < 0.01 versus sham) were not normalized by metformin treatment. In addition, ER stress markers were similarly increased in burn injury with or without metformin compared with sham (p < 0.05). We also found that gluconeogenesis and fatty acid metabolism gene expressions were upregulated with or without metformin compared with sham (p < 0.05). Our results indicate that, whereas thermal injury results in hepatic ER stress, metformin does not ameliorate postburn stress responses by correcting hepatic ER stress.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalMolecular Medicine
Volume19
Issue number1
DOIs
StatePublished - Jan 15 2013

    Fingerprint

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Hiyama, Y., Marshall, A. H., Kraft, R., Qa'aty, N., Arno, A., Herndon, D., & Jeschke, M. G. (2013). Effects of metformin on burn-induced hepatic endoplasmic reticulum stress in male rats. Molecular Medicine, 19(1), 1-6. https://doi.org/10.2119/molmed.2012.00330