Stimulation of glucagon secretion by gastric inhibitory polypeptide in patients with hepatic cirrhosis and hyperglucagonemia. Porcine gastric inhibitory polypeptide (GIP) was infused iv (120 micrograms in 60 min) in seven patients with biopsy-proven hepatic cirrhosis who had surgical porta-caval anastomoses and hyperglucagonemia in the postabsorptive state. The infusions resulted in elevation of blood levels of immunoreactive GIP into the upper range of those observed after ingestion of large mixed meals. This was accompanied by significant increments in immunoreactive glucagon (IRG) in the plasma. Similar infusions in two cirrhotic patients with surgical porta-caval anastomoses who had normal plasma IRG levels in the postabsorptive state had no effect on the plasma IRG level. Ingestion of triglyceride (60 g) in hyperglucagonemic cirrhotic patients with porta-caval anastomoses also resulted in elevation of plasma immunoreactive GIP, and this was again associated with significant elevation of the plasma IRG level. Chromatography studies showed that the increments in plasma IRG after the administration of GIP or triglyceride were largely accounted for by increases in pancreatic-type glucagon. There were no significant effects of administration of GIP or triglyceride on the blood levels of glucose or immunoreactive insulin. It is concluded that porcine GIP is glucagonotropic in patients with cirrhosis of the liver who show elevated levels of IRG in the plasma in the postabsorptive state. This effect is not due to diversion of portal blood to the systemic circulation and may be attributable to hypersensitivity of the alpha-cells to stimulation by GIP. 