Insulin levels after portal and systemic insulin infusion differ in a dose-dependent fashion

The role of the liver in the regulation of systemic insulin levels is not well understood. The reported extraction rates vary between 0 to 85%, and extraction of a constant fraction of 50% of the portally delivered insulin is generally assumed. In the present study, we have investigated the role of the liver in the regulation of systemic insulin levels in the normal rat. Insulin was infused into the portal vein of conscious and freely moving rats in doses of 20, 40, 80 pmol/min during 15 min to mimic the gradual release of insulin by the native endocrine rat pancreas. The profiles of plasma insulin and glucose levels in the systemic circulation were compared to those obtained after direct infusion into the systemic circulation. The effect of intraportal and direct systemic infusion on plasma insulin and blood glucose levels were virtually similar where 20 pmol/min was applied. But, these effects were different if the dose was 40 pmol/min, and this difference increased when the dose was increased to 80 pmol/min, since hypoglycemia was less severe and normoglycemia was restored more rapidly with portal than with systemic infusion. Thus, our results show that the fraction of intraportally infused insulin reaching the systemic circulation decreases with higher doses of insulin. This suggests that the liver contains adaptable mechanisms to reduce the systemic insulin levels.