Insulin action and secretion after surgical trauma : an experimental study in the rat

Abstract

Physical injury or surgical trauma leads to an endocrine-metabolic response that causes a catabolic state designed to promote the healing process. Insulin resistance and mobilization of endogenous fuel stores are prominent changes in metabolism seen after surgery. However, in profound and prolonged metabolic reactions to trauma, the continuous breakdown of body tissues to provide fuels may counteract the purpose of this response. The basic mechanisms underlying the initiation and maintenance of the changes in metabolism seen after physical injury are not fully understood.

The present studies were undertaken to investigate the mechanisms involved in the development of insulin resistance after surgical trauma. An experimental rat model of small bowel resection was developed for this purpose. Experiments were performed in rats 2 hours after surgical trauma and in non-traumatized controls. [3H]3-O-methylglucose transport in vitro and insulin signal transduction after in vivo or in vitro insulin-stimulation were determined in skeletal muscle. Insulin secretion was measured using in vivo and in vitro methodology and lipogenesis and lipolysis assessed in vitro in adipose tissue.

Finally, mRNA and protein levels of mitochondrial uncoupling protein (UCP) homologues in skeletal muscle and adipose tissue were determined. Surgical trauma resulted in reduced insulin-stimulated glucose transport and increased insulin stimulated PI 3-kinase activity. Glucose-stimulated insulin secretion was impaired in vivo and in vitro 2 h after surgery. Surgery did not affect arginine-stimulated insulin secretion, insulin content, or insulin mRNA expression. Insulin secretion in response to a glucose load and during a hyperglycemic clamp was normalized 4 h after surgical trauma. Insulin action on adipocyte lipogenesis and lipolysis was unaltered by surgical trauma. Two hours after surgery, concentrations of glucose, adrenaline and corticosterone were elevated and glycerol, NEFA and insulin were reduced in traumatized rats. UCP2 and UCP3 mRNA and protein levels increased in skeletal muscle 2 hours after bowel resection, whereas protein levels of UCP2 were unchanged postoperatively in adipose tissue.

In conclusion, posttraumatic insulin resistance in skeletal muscle is associated with reduced glucose transport but not with impaired insulin signaling to PI 3-kinase. Peripheral insulin resistance after surgical stress is due primarily to changes in skeletal muscle tissue. The effects of surgical trauma on the beta cell involve a temporary insensitivity to glucose. UCP homologues may be involved in the regulation of skeletal muscle substrate utilization in posttraumatic insulin resistance. The bowel resection model of surgical trauma provides a useful tool to further elucidate the molecular mechanism(s) underlying the development of insulin resistance and other physiological changes seen after surgical trauma.