Hepatic ischemia-reperfusion induces insulin resistance via down-regulation during the early steps in insulin signaling in rats.
BACKGROUND
The effects of hepatic ischemia-reperfusion (I/R) on insulin signaling remain unclear. We observed changes in insulin secretion and signal protein expression during the early steps in insulin signaling after hepatic I/R in rats.


METHODS
Eighty healthy Wistar rats were randomly divided into an I/R group and a control (C) group. After we exposed the hepatic hilum, ischemia was induced by clamping the hepatic artery and portal vein for 30 minutes and then the liver was reperfused for 2 hours in the I/R group; a show procedure was done in the C group. Blood samples were obtained after exposure of the hepatic hilum (T1) and 2 hours after reperfusion in the I/R group (T2) and 2.5 hours after T1 in the C group (T2). We measured glucose and insulin plasma concentrations. We determined the expressions of insulin signaling proteins, including insulin receptor (IR) beta unit (IR beta), IR substrate 1 (IRS-1), IRS-2, and P85 in phosphatidylinositol 3-kinase (PI3K) and tyrosine phosphorylation of these proteins in liver and skeletal muscle.


RESULTS
Plasma glucose concentrations increased in both groups at T2 (P < .01) and were higher in the I/R group (P < .01). Insulin concentrations in the I/R group did not change significantly at T2. Insulin concentrations at T2 were higher than those at T1 in the C group (P < .05). Expressions of insulin signal proteins showed no significant difference between the 2 groups; however, tyrosine phosphorylation of IR beta, IRS-1, IRS-2, and the interactions between IRS-1 in skeletal muscle or IRS-2 in liver and PI3K were significantly lower in the I/R group than the C group.


CONCLUSIONS
Hepatic I/R inhibited insulin secretion and induced insulin resistance via down-regulation during the early steps in insulin signaling in rats.
Liu
C
C
First Affiliated Hospital of Nanjing Medical University, The Liver Transplantation Center, Nanjing, Jiangsu, China. mingliu870@sohu.com
Wang
X
X
Chen
Z
Z
Zhang
L
L
Wu
Y
Y
Zhang
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000453:epidemiology; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins / Q000502:physiology; D007333:Insulin Resistance; D008099:Liver / Q000503:physiopathology*; D008102:Liver Circulation; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000502:physiology; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D015398:Signal Transduction
D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D011972:Receptor, Insulin