Glucose intolerance and hyperinsulinemia of cirrhosis are not results of spontaneous or surgical portosystemic shunting. To assess if spontaneous portosystemic shunting from collaterals contributes to the hyperinsulinemia of cirrhosis, 12 patients with alcoholic cirrhosis underwent a 5-hour oral glucose tolerance test 1 day before and 10 days after an elective side-to-side portacaval shunt. The glucose, insulin, and C peptide responses to oral glucose post-shunt were exaggerated but comparable to preoperative values. Compared with preoperative values, the fasting molar ratio of C peptide to insulin postoperatively had increased 40% (6.0 +/- 1.2 versus 8.4 +/- 0.7), indicating improved hepatic function. These results suggest that extrahepatic portosystemic shunting secondary to spontaneous splanchnic collaterals plays little or no role in the hyperinsulinemia of cirrhosis. It appears that decreased hepatic degradation of insulin in these patients is secondary to hepatocellular dysfunction rather than a result of shunting of portal blood around the liver. 