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.
Key words
hyperglycemia - insulin resistance - trauma - insulin receptor substrate
