Insulin Protects against Hepatic Damage Postburn

Abstract

Burn injury causes hepatic dysfunction associated with endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR). ER stress/UPR leads to hepatic apoptosis and activation of the Jun-N-terminal kinase (JNK) signaling pathway, leading to vast metabolic alterations. Insulin has been shown to attenuate hepatic damage and to improve liver function. We therefore hypothesized that insulin administration exerts its effects by attenuating postburn hepatic ER stress and subsequent apoptosis. Male Sprague Dawley rats received a 60% total body surface area (TBSA) burn injury. Animals were randomized to receive saline (controls) or insulin (2.5 IU/kg q. 24 h) and euthanized at 24 and 48 h postburn. Burn injury induced dramatic changes in liver structure and function, including induction of the ER stress response, mitochondrial dysfunction, hepatocyte apoptosis, and upregulation of inflammatory mediators. Insulin decreased hepatocyte caspase-3 activation and apoptosis significantly at 24 and 48 h postburn. Furthermore, insulin administration decreased ER stress significantly and reversed structural and functional changes in hepatocyte mitochondria. Finally, insulin attenuated the expression of inflammatory mediators IL-6, MCP-1, and CINC-1. Insulin alleviates burn-induced ER stress, hepatocyte apoptosis, mitochondrial abnormalities, and inflammation leading to improved hepatic structure and function significantly. These results support the use of insulin therapy after traumatic injury to improve patient outcomes.

Simvastatin Protects Hepatocytes From Apoptosis by Suppressing the TNF-α/Caspase-3 Signaling Pathway in Mice With Burn Injury

“…Hepatic apoptosis has been recognized as part of the pathological changes after burn injury [28, 29]. High apoptotic cell number after burn injury implicates hepatic damage and impairment to its function.…”

Burn Plus Lipopolysaccharide Augments Endoplasmic Reticulum Stress and NLRP3 Inflammasome Activation and Reduces PGC-1α in Liver

“…A well-established method was used to induce a full-thickness scald burn (13, 14). The treatment groups included sham, sham + LPS, burn, and burn + LPS.…”

Alcohol Modulation of the Postburn Hepatic Response

“…More aggressive control results in suppression of hepatic glucose release, lower systemic glucose levels, decreased incidence of urinary tract infections and mortality when compared to conventional goals of blood glucose <215mg/dL [145]. Animal models have demonstrated that insulin therapy decreases hepatic ER stress, attenuates expression of pro-inflammatory mediators such as IL-6, monocyte chemoattractant protein-1 (MCP-1), and cytokine-induced neutrophil chemoattractant-1 (CINC-1), and reverses structural and functional changes in hepatocyte mitochondria [146]. …”