ABSTRACT
Liver cirrhosis (LC) and insulin resistance (IR) are closely correlated, clinically presenting hyperglycemia, hyperinsulinism, hyperlipidemia and high cytokines levels, however, the underlying mechanism is not completely clear. Recent reports show that insulin receptor substrate-1 (IRS-1) is associated with IR in LC. IRS-1 plays a pivotal role on insulin signal transduction; it changes insulin signaling by up-or down-regulating of protein presentation, post-translational modification and subcellular localization of proteins, particularly in phosphorylation/dephosphorylation of post-translational modification. Furthermore, LC with different etiology may have different mechanism of IRS-1 effect on IR.
Subject(s)
Insulin Receptor Substrate Proteins/physiology , Insulin Resistance , Liver Cirrhosis/metabolism , Humans , Insulin/metabolism , Insulin Receptor Substrate Proteins/metabolismABSTRACT
Decreased glucose tolerance and diabetes are frequently observed in advanced liver cirrhosis patients and may be related to insulin resistance. Glucose transporter-4 (GLUT4), one of the most important glucose transporters, plays a key role in the development of type 2 diabetes. In order to study the mechanism of insulin resistance in liver cirrhosis patients, we measured the insulin sensitivity index and determined the GLUT4 protein and mRNA contents of skeletal muscle by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively, in normal people and liver cirrhosis patients. The results showed that the levels of glucose, insulin, and C-peptide in two liver cirrhosis groups were higher and the insulin sensitivity index lower than those of the normal control group. The sensitivity of insulin may decrease with the decline of liver function. However, the contents of GLUT4 protein and mRNA in patients with advanced liver cirrhosis were similar to those of normal controls. In conclusion, insulin resistance is observed in patients with advanced liver cirrhosis but may not be correlated with the skeletal contents of GLUT4 protein and mRNA.