AIM:Gastric inhibitory polypeptide is secreted fromintestinal K-cells in response to nutrient ingestion andacts as an incretin hormone in human physiology.Whileanimal experiments suggested a role for GIP as aninhibitor of gastric secretion,the GIP effects on gastricacid output in humans are still controversial.METHODS:Pentagastrin was administered at an infusionrate of 1 μg.kg~(-1).h~(-1)over 300 min in 8 patients withtype 2 diabetes(2 female,6 male,54+10 years,BMI30.5+2.2 kg/m~2;no history of autonomic neuropathy)and 8 healthy subjects(2/6,46±6 years.,28.9±5.3 kg/m~2).A hyperglycaemic clamp(140 mg/dl)was performedover 240 min.Placebo,GIP at a physiological dose(1pmol.kg~(-1).min~(-1)),and GIP at a pharmacological dose(4 pmol.kg~(-1).min~(-1))were administered over 60 mineach.Boluses of placebo,20 pmol GIP/kg,and 80 pmolGIP/kg were injected intravenously at the beginning ofeach infusion period,respectively.Gastric volume,acidand chloride output were analysed in 15-min intervals.Capillary and venous blood samples were drawn for thedetermination of glucose and total GIP.Statistics werecarried out by repeated-measures ANOVA and one-wayANOVA.RESULTS:Plasma glucose concentrations during thehyperglycaemic clamp experiments were not different between patients with type 2 diabetes and controls.Steady-state GIP plasma levels were 61±8 and 79±12pmol/l during the low-dose and 327±35 and 327±17pmol/l during the high-dose infusion of GIP,in healthycontrol subjects and in patients with type 2 diabetes,respectively(P=0.23 and p 0.99).Pentagastrin markedlyincreased gastric acid and chloride secretion(P<0.001).There were no significant differences in the rates ofgastric acid or chloride output between the experimentalperiods with placebo or any dose of GIP.The temporalpatterns of gastric acid and chloride secretion weresimilar in patients with type 2 diabetes and healthycontrols(P=0.86 and P=0.61,respectively).CONCLUSION:Pentagastrin-stimulated gastric acidsecretion is similar in patients with type 2 diabetes andhealthy controls.GIP administration does not influencegastric acid secretion at physiological or pharmacologicalplasma levels.Therefore,GIP appears to act as anincretin rather than as an enterogastrone in humanphysiology. AIM: Gastric inhibitory polypeptide is secreted fromintestinal K-cells in response to nutrient ingestion and indicators as an incretin hormone in human physiology. Whileanimal experiments suggested a role for GIP as an inhibitor of gastric secretion, the GIP effects on gastricacid output in humans are still controversial. METHODS: Pentagastrin was administered at an infusion rate of 1 μg.kg -1 (h -1) over 300 min in 8 patients with type 2 diabetes (2 female, 6 male, 54 + 10 years, BMI 30.5 + 2.2 kg / m 2; no history of autonomic neuropathy) and 8 healthy subjects (2/6, 46 ± 6 years, 28.9 ± 5.3 kg / m 2). A hyperglycaemic clamp (140 mg / dl) was performed over 240 min.Placebo, GIP at a physiological dose (1 pmol.kg ~ (-1) .min ~ (-1)), and GIP at a pharmacological dose (4 pmol.kg ~ (-1) .min ~ (-1) ) were administered over 60 miners. Bank of placebo, 20 pmol GIP / kg, and 80 pmolGIP / kg were injected intravenously at the beginning of of infusion period, respectively. Gastric volume, acid and chloride output were analyzed in 15-min intervals. Capi llary and venous blood samples were drawn for the determination of glucose and total GIP. Statistics werecarried out by repeated-measures ANOVA and one-way ANOVA .RESULTS: Plasma glucose concentrations during the hyperglycaemic clamp experiments were not different between patients with type 2 diabetes and controls .teady -state GIP plasma levels were 61 ± 8 and 79 ± 12 pmol / l during the low-dose and 327 ± 35 and 327 ± 17 pmol / l during the high-dose infusion of GIP, in healthy subjects and in patients with type 2 diabetes, respectively (P = 0.23 and p 0.99). Pentagastrin markedly reinforced gastric acid and chloride secretion (P <0.001). There was no significant differences in the rates of gastric acid or chloride output between the experimental cycles with placebo or any dose of GIP. temporal patterns of gastric acid and chloride secretion weresimilar in patients with type 2 diabetes and healthy controls (P = 0.86 and P = 0.61, respectively) .CONCLUSION: Pentagastrin-stimulated gastric acid secretion is simila r in patients with type 2 diabetes andhealthy controls. GIP administration does not influencegastric acid secretion at physiological or pharmacologicalplasma levels. Before, GIP appears to act as anincretin rather than as an enterogastrone in humanphysiology.