The effect of insulin and glucose on fat-induced gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1 (7-36 amide)) was studied in five healthy subjects during continuous glucose infusion (Protocol 1) and during hyperinsulinaemic euglycaemic blood glucose clamp (Protocol 2). In Protocol 1, 50 g fat was orally ingested and glucose was infused at a rate of 0.7 g/kg/h for 2 h continuously from the time of fat ingestion. Either glucose infusion alone or fat ingestion alone was carried out in the same subjects as the control. The release of GIP and GLP-1 (7-36 amide) was suppressed in the hyperglycaemic hyperinsulinaemic state. In protocol 2, 50 g of fat was ingested and insulin was infused at a rate of 0.1 U/kg/h with an artificial pancreas system to obtain the normoglycaemic hyperinsulinaemic state. The release of GIP was significantly suppressed in the normoglycaemic hyperinsulinaemic state as well as in the hyperglycaemic hyperinsulinaemic state. However, the release of GLP-1 (7-36 amide) was suppressed in the hyperglycaemic hyperinsulinaemic state but not in the euglycaemic hyperinsulinaemic state. Thus, it is concluded that insulin inhibits fat-induced GIP, but not GLP-1 (7-36 amide), secretion and that glucose is likely to inhibit GLP-1 (7-36 amide) secretion.