Skeletal muscle insulin resistance after trauma: insulin signaling and glucose transport

Am J Physiol. 1998 Aug;275(2):E351-8. doi: 10.1152/ajpendo.1998.275.2.E351.

Abstract

Surgical trauma induces peripheral insulin resistance; however, the cellular mechanism has not been fully elucidated. We examined the effects of surgical trauma on insulin receptor signaling and glucose transport in skeletal muscle, a tissue that plays a predominant role in maintaining glucose homeostasis. Surgical trauma was induced by intestinal resection in the rat. Receptor phosphorylation was not altered with surgical trauma. Phosphotyrosine-associated phosphatidylinositol (PI) 3-kinase association was increased by 60 and 82% compared with fasted and fed controls, respectively (P < 0. 05). Similar results were observed for insulin receptor substrate-1-associated PI 3-kinase activity. Insulin-stimulated protein kinase B (Akt kinase) phosphorylation was increased by 2.2-fold after surgical trauma (P < 0.05). The hyperphosphorylation of Akt is likely to reflect amplification of PI 3-kinase after insulin stimulation. Submaximal rates of insulin-stimulated 3-O-methylglucose transport were reduced in trauma vs. fasted rats by 51 and 38% for 100 and 200 microU/ml of insulin, respectively (P < 0.05). In conclusion, insulin resistance in skeletal muscle after surgical trauma is associated with reduced glucose transport but not with impaired insulin signaling to PI 3-kinase or its downstream target, Akt. The surgical trauma model presented in this report provides a useful tool to further elucidate the molecular mechanism(s) underlying the development of insulin resistance after surgical trauma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism*
  • Eating
  • Epinephrine / blood
  • Fasting
  • Fatty Acids, Nonesterified / blood
  • Glucose / metabolism*
  • Hydrocortisone / blood
  • Insulin / blood
  • Insulin Receptor Substrate Proteins
  • Insulin Resistance / physiology*
  • Lactates / blood
  • Male
  • Muscle, Skeletal / physiology
  • Muscle, Skeletal / physiopathology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Surgical Procedures, Operative
  • Wounds and Injuries / blood
  • Wounds and Injuries / physiopathology*

Substances

  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • Lactates
  • Phosphoproteins
  • Phosphatidylinositol 3-Kinases
  • Glucose
  • Hydrocortisone
  • Epinephrine