[Research of the relationship between insulin signal transduction and glucose transportation in rats after trauma].

OBJECTIVE

To investigate the relationship between insulin post-receptor signal transduction and the change of glucose transportation by skeleton muscle after surgical trauma in rats.

METHODS

Small intestine bowel resection was performed to establish the surgical trauma model in rats. The content and the phosphorylation state of two key proteins in the insulin signaling pathway: insulin receptor substrate-1 (IRS-1) and protein kinase B (PKB/Akt) in skeletal muscle were measured respectively. The 3H labeled glucose uptake experiment was carried out to evaluate the glucose transportation function in both groups. Finally, the expression and the distribution of glucose transporter 4 (GLUT4) in skeletal muscle were detected respectively.

RESULTS

The total content of IRS-1 and PKB/Akt in skeletal muscle in both groups had no difference. The phosphorylation of tyrosine (Tyr) residue of IRS-1 in the operation group was attenuated by 31% (P = 0.018), whereas the phosphorylation of serine (Ser) residue of IRS-1 was significantly enhanced by 63% compared with the control group (P = 0.000). Accordingly, the phosphorylation state of PKB/Akt (activated) was attenuated by 48% in the operation group (P = 0.000). The rate of 2-Deoxy-D-[1-3H] glucose transported by skeletal muscle in the operation group was significantly lower than that in the control group. Both the expressions of GLUT-4 mRNA and the total content of GLUT-4 protein in two groups had no significant difference. But the expression of GLUT4 in the plasma membrane was decreased in the operation group than that in the control group.

CONCLUSIONS

Insulin resistance was associated with enhanced Ser phosphorylation of IRS-1, which impaired its interaction with its downstream target PKB/Akt. Such impaired interactions abolished the ability of IRS-1 to undergo insulin-induced Tyr phosphorylation and further propagate the insulin receptor signal. Uncoupling of signal transduction led to decrease in glucose uptake which associated with a defect in insulin-stimulated glucose transport and GLUT-4 translocation.