The Study On The Role Of IRS-1in Insulin Resistance Of Islet Cells Following Cardiopulmonary Bypass In The Rabbit Model

Objective To observe the mediated control of IRS-1and insulinresistance in islet cells of rabbits and investigate the potential mechanism ofhyperglycemia in cardiopulmonary bypass(CPB).Methods Thirty-five New Zealand rabbits(clean class) of bodyweight2.8±0.3kg were divided randomly into sham operation (Sham, n=5)and CPB (CPB, n=30) groups. Rabbit model of CPB was established byusing the rabbits in CPB group. Rabbits in Sham group only open the chest.It was vital to make the maintenance of anesthesia steady during CPB. Thearterial blood samples of rabbits in the two groups were collected at5minafter narcosis (T0), immediately before CPB (T1), immediately after aorticcross-clamping (T2), as well as5(T3),35(T4) and75min (T5) afterreperfusion and determined for blood glucose by glucometer and for insulinand glucagon by radioimmunoassay and assessed insulin resistance (IR)level by the homeostasis model assessment insulin resistance index (IRI).After the rabbits in CPB group were sacrificed by the corresponding times(T0~5), pancreatic tissues were got. The expressions of insulin, glucagon and IRS-1in islets were detected by immunofluorescence assays and laserconfocal fluorescence microscopy.Results (1) Biochemistry indexes in plasma: Compared with thebaseline at T0, Plasma concentrations of glucose levels and IRI at T1~5,insulin levels at T2~5of the two groups increased significantly (P<0.05),plasma glucagon concentrations significantly decreased at T1~5in groupSham and increased at T4~5in group CPB (P<0.05). Plasma concentrationsof glucose, insulin, glucagon levels and IRI at T2~5were significantly higherin CPB group than in Sham group (P<0.05).(2) The immunofluorescent indexes in pancres islet: Compared withthe baseline value at T0, the expression of IRS-1in islets at T1and theexpression of GLC in islets at T3~5significantly decreased (P<0.05);Compared with the data at T1, the expression of INS in islets at T5and theexpression of IRS-1in islets at T2significantly increased, the expression ofGLC in islets significantly decreased at T3~5(P<0.05); Compared with thedata at T2, the expression of INS in islets at T3, the expression of IRS-1inislets at T4~5and the expression of GLC in islets at T3~5significantlydecreased (P<0.05); Compared with the data at T3, the expression of INS inislets significantly increased at T5and the expression of GLC in isletssignificantly decreased at T5(P<0.05); Compared with the data at T4, theexpression of INS in islets significantly increased at T5(P<0.05).（3）Data normalization: Compared with the baseline value at T0, the ratio between INS in islets and blood glucose level, the ratio between IRS-1in islets and blood glucose level, the ratio between GLC in islets and bloodglucose level significantly decreased at T1~5(P<0.05); Compared with thedata at T1, three ratios significantly decreased at T2~5(P<0.05); Comparedwith the data at T2, the ratio between INS in islets and blood glucose levelat T3, the ratio between IRS-1in islets and blood glucose level decreased atT3~4, the ratio between GLC in islets and blood glucose level at T3~5significantly decreased (P<0.05); Compared with the data at T3~4, the ratiobetween INS in islets and blood glucose level, the ratio between IRS-1inislets and blood glucose level significantly increased at T5(P<0.05).(4) The ratio of IRS-1-INS in islets: Compared with the data at T0, theratio of IRS-1-INS in islets significantly decreased at T1, T5(P<0.05);Compared with the data at T1, the ratio significantly increased at T2~3(P<0.05); Compared with the data at T2~3, the ratio significantly decreased atT4~5(P<0.05); Compared with the data at T4, the ratio significantly decreasedat T5(P<0.05).Conclusion (1) Peripheral insulin resistance is resulted fromcardiopulmonary bypass, and reachs its peak after reperfusion underanesthetized condition.(2) The relative lack of IRS-1expression in isletduring CPB, resulting in insulin resistance of islet β-cell.(3) Abnormalhypersecretion of glucagon in hyperglycemia could be the result of insulinresistance of islet α-cell in CPB.