Acute insulin resistance following surgical trauma in rats

Exp Clin Endocrinol Diabetes. 2012 Jun;120(6):315-22. doi: 10.1055/s-0031-1295423. Epub 2011 Dec 20.

Abstract

Objective: To unravel the possible mechanism of acute posttraumatic insulin resistance in rats.

Methods: Resection of small intestine was performed to establish the surgical trauma model. The blood glucose and serum insulin level were detected and the HOMA index was calculated. The Hyperinsulinemic-euglycemic clamp was performed to investigate the glucose disposal rate by peripheral tissue. The content and phosphorylation state of IRS-1, p85 of PI3-K and PKB/Akt in skeletal muscle were measured respectively. Finally, the [3H] labeled glucose uptake experiment was carried out.

Results: The blood glucose elevated significantly after resection of small intestine in rats. The level of serum insulin decreased during the first 30 min after operation but elevated in the following time. The HOMA-IR in trauma group was significantly greater than control group; however the HOMA-β in trauma group was less than control group. The glucose disposal rate was decreased 49% after operation. The p-IRS-1(Ser307) was significantly enhanced 95% after trauma while the p-IRS-1 (Tyr612) was attenuated by 38%. The phosphorylation of its downstream target, p-PKB/Akt(Ser473) was attenuated by 48%. Accordingly, the glucose uptaken by skeletal muscle was significantly decreased in trauma group.

Conclusion: We demonstrated the posttraumatic insulin resistance occurred soon after surgical trauma in rats. The level of insulin was relatively insufficient because of the decreased sensitivity in peripheral tissue. Trauma induced Ser phosphorylation instead of Tyr phosphorylation eliminated the ability of IRS-1 to activate downstream effector molecules such as PKB/Akt and resulted in severe impairment of insulin signal transduction and glucose transport in skeletal muscle.

Publication types

  • Comparative Study

MeSH terms

  • Acute Disease
  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Disease Models, Animal
  • Glucose / pharmacokinetics
  • Glucose Clamp Technique
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Resistance / physiology*
  • Male
  • Postoperative Complications / metabolism*
  • Postoperative Complications / pathology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Wounds and Injuries / complications
  • Wounds and Injuries / etiology
  • Wounds and Injuries / metabolism*
  • Wounds and Injuries / pathology

Substances

  • Blood Glucose
  • Insulin
  • Glucose