Mechanism of insulin resistance and hyper-insulinemia in fatty liver.

Hyperinsulinemia and insulin resistance are common features seen in most liver diseases. The present study was carried out on an experimental model of fatty liver (tetracycline induced) in albino rats. Significantly elevated levels of both peripheral plasma insulin and plasma glucose concentrations were recorded in both the fasting state and after an oral glucose intake in the tetracycline-treated rats. The presence of hyperinsulinemia accompanying hyperglycemia is considered a sign of insulin resistance. Peripheral insulin resistance has been proved in this work by the reduced "A" value which refer to the peripheral insulin activity (sensitivity) in fatty liver rats compared to normal rats. The hyperinsulinemia recorded here was due to pancreatic hypersecretion and not a result of reduced hepatic degradation. Hypersecretion of insulin was clearly determined by measuring the level of immunoreactive insulin (IRI) in pancreatic vein which exhibited a significant rise in tetracycline-treated rats, and there was a positive correlation between the pancreatic venous and peripheral venous insulin in the basal state and after 30 min. of oral glucose administration. Hepatic degradation of insulin was not a cause as evidenced by First: the amount of insulin secreted and insulin consumed were significantly higher in fatty liver rats than normal controls. Second: the whole body extraction ratio or insulin degradation was not significantly different in the tetracycline-treated rats from the normal rats. The present data suggests that insulin resistance and hyperinsulinemia underlie the observed metabolic disturbances that characterize fatty liver disease.