Polytrauma-induced hepatic stress response and the development of liver insulin resistance

Abstract

Insulin resistance and metabolic dysfunction are common following injury. Polytrauma is defined as combined injuries to more than one body part or organ system, and is common in modern warfare, as well as automobile and industrial accidents. Polytrauma can include any combination of burn injury, fracture, hemorrhage, trauma to the extremities, and blunt or penetrating trauma. Multiple minor injuries are often more deleterious than a more severe single injury. To investigate the mechanisms of development of insulin resistance following injury, we have developed a rat model of polytrauma which combined soft tissue trauma with burn injury and penetrating gastrointestinal (GI) trauma. Male Sprague-Dawley rats were subjected to a laparotomy plus either a 15-18% total body surface area scald burn or a single puncture of the cecum (CLP) with a G30 needle, or the combination of both burn and CLP injuries (polytrauma). We examined the effects of polytrauma which increased markers of hepatic endoplasmic reticulum (ER) stress, and increased hepatic Trib3 mRNA levels coincident with reduced insulin-inducible insulin signaling. Phosphorylation/activation of the insulin receptor (IR) and AKT were decreased at 24, but not 6h following polytrauma. These results demonstrate a complex, time-dependent development of hepatic ER-stress and a diminished response to insulin, which were among the pathological sequelae following polytrauma.

Modeling trauma in rats: similarities to humans and potential pitfalls to consider

“…Therefore, the authors confirmed that models utilizing combinatorial injuries are needed to more accurately model the human condition. Another polytrauma model includes animals that were subjected to a laparotomy plus burn and single puncture of the cecum injuries [165]. The authors concluded from their data that their model of polytrauma is straightforward to perform and highly reproducible, making it a useful model for studying the multifaceted early pathophysiology following polytrauma.…”

“…The authors concluded from their data that their model of polytrauma is straightforward to perform and highly reproducible, making it a useful model for studying the multifaceted early pathophysiology following polytrauma. Furthermore, they provided evidence that using a double-hit model to represent polytrauma is of limited validity, because the findings again suggest a complex pathophysiological response to polytrauma, and indicate that the mechanisms leading to the development of insulin resistance vary depending upon the type of injury [165]. Interestingly, their data are unlike those found in more severe single-injury models or those observed following the combination of trauma and hemorrhage.…”

Effects of preoperative oral administration of glucose solution combined with postoperative probiotics on inflammation and intestinal barrier function in patients after colorectal cancer surgery

“…Previous studies have revealed that the treatment combined with probiotics after liver transplantation and other abdominal operations shortens the application time of antibiotics and significantly reduces the incidence rate of infection (22). In this study, the incidence rates of incision infection and hypoproteinemia were similar in both groups (P>0.05).…”

Polytraumatic injury with splenic rupture and unilateral avascular renal necrosis: A case report

“…2 Interestingly, polytrauma has also been associated with severe systemic manifestations including hepatic dysfunction and insulin resistance. 3 In this paper, we present a patient who underwent an emergency exploratory laparotomy status post MVC leading to splenic injury, avascular necrosis of kidney and right upper extremity Colles' fracture. Goal of the paper is to present a patient of polytrauma along with its proper treatment plan in terms of prioritizing the standard of care.…”