Hepatic insulin extraction after major hepatectomy.

Abstract

After major hepatectomy, the remaining liver compensates for its reduced mass and maintains euglycemia through increased hepatic glucose output. The mechanism of this compensation may be a diminished hepatic extraction of portal insulin, which thereby decreases the suppressive effects of insulin on gluconeogenesis. Extraction of insulin by the liver was measured using the isolated perfused rat liver model. Fasted Sprague-Dawley rats were studied at 1, 2, 3, 4, 6, and 14 days after 70% hepatectomy. Control rats had no operation, and sham rats were studied 1 day after a sham laparotomy. The difference between portal and caval insulin concentrations was determined and reported as micromoles of insulin extracted per gram liver per minute. Insulin extraction decreased from 191 +/- 22 microU/gm liver/min in control rats to 87 +/- 13.2 microU/gm liver/min at postoperative day 1 (p = 0.0001). Extraction normalized by postoperative day 6. Extraction rates in rats recovering from sham laparotomy were similar to control rats (p = 0.088), suggesting that decreased extraction in hepatectomized rats was not due to postoperative stress. After 70% hepatectomy, the remaining liver extracts less insulin per gram. This may explain the ability of the reduced liver mass to maintain euglycemia after major hepatectomy.