Influence of gastric inhibitory polypeptide on pentagastrin-stimulated gastric acid secretion in patients with type 2 diabetes and healthy controls

Abstract

Aim: Gastric inhibitory polypeptide is secreted from intestinal K-cells in response to nutrient ingestion and acts as an incretin hormone in human physiology. While animal experiments suggested a role for GIP as an inhibitor of gastric secretion, the GIP effects on gastric acid output in humans are still controversial.

Methods: Pentagastrin was administered at an infusion rate of 1 microg . 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 min each. Boluses of placebo, 20 pmol GIP/kg, and 80 pmol GIP/kg were injected intravenously at the beginning of each infusion period, respectively. Gastric volume, acid and chloride output were analysed in 15-min intervals. Capillary and venous blood samples were drawn for the determination of glucose and total GIP. Statistics were carried 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. Steady-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 control subjects and in patients with type 2 diabetes, respectively (P=0.23 and P=0.99). Pentagastrin markedly increased gastric acid and chloride secretion (P< 0.001). There were no significant differences in the rates of gastric acid or chloride output between the experimental periods with placebo or any dose of GIP. The temporal patterns of gastric acid and chloride secretion were similar in patients with type 2 diabetes and healthy controls (P=0.86 and P=0.61, respectively).

Conclusion: Pentagastrin-stimulated gastric acid secretion is similar in patients with type 2 diabetes and healthy controls. GIP administration does not influence gastric acid secretion at physiological or pharmacological plasma levels. Therefore, GIP appears to act as an incretin rather than as an enterogastrone in human physiology.

Figure 1

Plasma concentrations of glucose (A), glucose infusion rates (B) and plasma concentrations of total GIP (C) during hyperglycemic clamp experiments with the intravenous infusion of pentagastrin (1 µg . kg^-1 . h^-1; -90 to 210 min), placebo (0 - 60 min), GIP at a low dose (1 pmol . kg^-1 . min^-1; 60-120 min), and GIP at a high dose (4 pmol . kg^-1 . min^-1; 120 -180 min) in eight patients with type 2 diabetes (open circles) and eight healthy controls (filled diamonds). Arrows indicate bolus administrations of placebo, 20 pmol GIP/kg and 80 pmol GIP/kg, respectively. Data are presented as means ± SEM; P-values were calculated using repeated measures ANOVA and one-way ANOVA and denote A: differences between the groups, B: differences over time and AB: differences due to the interaction of group and time. ^aP < 0.05 patients with type 2 diabetes at individual time points.

Figure 2

Gastric volume (A), as well as gastric acid (B) and chloride (C) concentrations determined in 15-min intervals in eight patients with type 2 diabetes (open circles) and eight healthy controls (filled diamonds) studied during hyperglycemic clamp experiments with the intravenous infusion of pentagastrin (1 µg . kg^-1 . h^-1; -90 to 210 min), placebo (0 - 60 min), GIP at a low dose (1 pmol . kg^-1 . min^-1; 60-120 min), and GIP at a high dose (4 pmol . kg^-1 . min^-1; 120 -180 min). Arrows indicate bolus administrations of placebo, 20 pmol GIP/kg and 80 pmol GIP/kg, respectively. Data are presented as means ± SEM; P -values were calculated using repeated measures ANOVA and one-way ANOVA and denote A: differences between the groups, B: differences over time and AB: differences due to the interaction of group and time.

Figure 3

Gastric acid (A), and chloride (B) secretion rates per 15 min in eight patients with type 2 diabetes (open circles) and eight healthy controls (filled diamonds) studied during hyperglycemic clamp experiments with the intravenous infusion of pentagastrin (1 µg . kg^-1 . h-¹; -90 to 210 min), placebo (0 - 60 min), GIP at a low dose (1 pmol . kg^-1 . min^-1; 60-120 min), and GIP at a high dose (4 pmol . kg^-1 . min^-1; 120 -180 min). Arrows indicate bolus administrations of placebo, 20 pmol GIP/kg and 80 pmol GIP/kg, respectively. Data are presented as means± SEM; p-values were calculated using repeated measures ANOVA and one-way ANOVA and denote A: differences between the groups, B: differences over time and AB: differences due to the interaction of group and time.