[Impairments of insulin receptor function in insulin resistant states].

Type 2 diabetes is characterized by insulin resistance in skeletal muscle. Since the molecular mechanism of insulin resistance is still unknown, insulin receptor dysfunction including abnormal IRS-1 phosphorylation is considered to be responsible for insulin resistance in some pathological states. Obesity is one of major factors to induce insulin receptor dysfunction. Regarding the mechanism of insulin resistance related obesity, the increased expression of Tumor necrosis factor alpha and abnormality in PTPase in skeletal muscle are postulated. As well as obesity, prolonged hyperglycemia, dyslipidemia and hypertension also induce the impairment of insulin receptor function. Therefore, the enhancement of insulin sensitivity by modulating these factors is a possible treatment modality in insulin resistant states.