Effects of metformin on burn-induced hepatic endoplasmic reticulum stress in male rats.
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.
Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Yaeko
Y
Hiyama
Alexandra H
AH
Marshall
Robert
R
Kraft
Nour
N
Qa'aty
Anna
A
Arno
David N
DN
Herndon
Marc G
MG
Jeschke
D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000418:Albumins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy*; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D015854:Up-Regulation
D000418:Albumins; D005227:Fatty Acids; D008687:Metformin; D000410:Alanine Transaminase