| Background and ObjectiveInsulin resistance is a common pathological state in which target tissues fail to respond properly to normal levels of circulating insulin. Metabolic stress after surgery is always associated with alterations in carbohydrate metabolism characterized by the impairment in insulin-stimulated glucose disposal, which is named posttraumatic insulin resistance.Recent studies show that the development of posttraumatic insulin resistance is proportional to the magnitude of operation but negatively correlated to the prognosis.However, the molecular bases underlying posttraumatic insulin resistance still remain unclarified. At present, to clarify the mechanism of post-traumatic insulin resistance, reducing or preventing insulin resistance, reduce the occurrence of clinical adverse events and improve prognosis in patients with research focus.Studies have shown that as a specific cytokine that fat cells secreted, adiponectin has anti-inflammatory, anti-atherosclerosis and other effects, the most noteworthy is its role in improving insulin resistance.However,there are few reseaches report the improving effect of the posttraumatic insulin resistance.The purpose of this study is to provide and unravel the mechanism of posttraumatic insulin resistance.Aslo to confirm that adiponectin can improve posttraumatic insulin resistance and try to explain the possible mechanisms.To accomplish this goal, small intestine bowel resection was performed to establish the surgical trauma model in rats. Adiponectin was preused in one group,the others was not.We previously used this model to investigate whether insulin sensitivity is affected by operation. Then we studied posttraumatic alterations in insulin signaling in skeletal muscle.Methods60 clean male Sprague-Dawley rats (200-250g) were randomized into two groups, the adiponectin group(n=20) the operation group (n=20) and the control group (n=20). Small intestinal resection was performed in the adiponectin group and the operation group.In the adiponectin group we injected adiponectin to the rats by lmg/kg before 2h of the operation. The control animals underwent anesthesia only. The following two different sets of experiments were performed.(1)Blood samples were obtained for determination of the level of blood glucose, serum insulin. Then the HOMA-IR index and the HOMA-βindex were calculated.(2)Several key proteins in the insulin signaling such as insulin receptor substrate 1(IRS-1),protein kinase B (PKB/AKT) in skeletal muscle were measured respectively.Results1.The level of blood glucose elevated significantly after small bowel resection in rats.The level of serum insulin decreased 30min after operation but elevated in the following time.In the adiponectin group the level of blood glucose decreased significantly compared with the the operation group,and the level of serum insulin had no difference between the two groups.2.The index of insulin resistance (HOMA-IR) in the operation group was significantly greater than in the control group, while the index of insulin secretion (HOMA-β) in the operation group was less than in the control group. In the adiponectin group,while HOMA-IR was significantly less than in the operation group and HOMA-βwas greater than in the operation group.3.The total content of IRS-1 in skeletal muscle in groups of operation-control and adiponectin-operation had no difference (247.43±6.08%vs.246.42±4.84%, F=0.031,P=0.782)and(245.10±4.46%vs.247.43±6.08%,F=0.156,P=0.509). The phosphorylation of tyrosine (Tyr) residue of IRS-1 seen in the operation group was attenuated by 31%(88.54±33.48 vs.128.60±33.19,F=0.108,P=0.000), whereas the phosphorylation of serine (Ser) residue of IRS-1 was significantly enhanced by 64%(154.31±36.94 vs.94.20±27.88,F=0.602,P=0.000) compared with the control group. In the adiponectin group compared with the operation group, the phosphorylation of tyrosine (Tyr) residue of IRS-1 was enhanced by 23%(109.05±30.77vs.88.54±33.48,F=0.012,P=0.000),where as the phosphorylation of serine (Ser) residue of IRS-1 was significantly attenuated by 30%(118.65±33.49vs.154.31±36.94,F=0.272,P=0.000)。4.The total content of PKB/Akt in skeletal muscle in groups of operation-control and adiponectin-operation had no difference(116.95±2.03%vs.116.20±3.49%, F=0.403,P=0.688)and (116.45±3.56%vs.116.95±2.03%,F=0.613,P=0.793).Yet the phosphorylation state of PKB/Akt (activated) was attenuated by 46% in the operation group (46.58±2.48 vs.86.32±3.31,F=0.153,P=0.000).On the contrary the phosphorylation state of PKB/Akt (activated) was enhanced by 56% in the adiponectin group compared with the operation group(72.73±2.95vs.46.58±2.48, F=0.473,P=0.000). ConclusionsIn conclusion, we demonstrated that small intestinal resection can be ensured to establish the animal model of posttraumatic insulin resistance and adiponectin was preused.The surgical trauma induced marked alterations in glucose metabolism during the immediate postoperative period. The later appearance of elevated serum insulin argued against the opinion that secretion of insulin was reduced after trauma. The research on insulin signaling suggested that insulin resistance was associated with enhanced Ser phosphorylation of IRS-1,which impaired its interaction with PKB/Akt. Such impaired interactions abolished the ability of IRS-1 to undergo insulin-induced Tyr phosphorylation and further propagate the insulin receptor signal.Adiponectin can alleviate the above-mentioned ways and improve post-traumatic insulin resistance which resulting high blood sugar. |
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