Basic Research
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World J Gastroenterol. Mar 28, 2006; 12(12): 1874-1880
Published online Mar 28, 2006. doi: 10.3748/wjg.v12.i12.1874
Influence of gastric inhibitory polypeptide on pentagastrin-stimulated gastric acid secretion in patients with type 2 diabetes and healthy controls
Juris J Meier, Michael A Nauck, Bartholomaeus Kask, Jens J Holst, Carolyn F Deacon, Wolfgang E Schmidt, Baptist Gallwitz
Juris J Meier, Bartholomaeus Kask, Wolfgang E Schmidt, Baptist Gallwitz, Department of Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Germany
Michael A Nauck, Diabeteszentrum Bad Lauterberg, Germany
Jens J Holst, Carolyn F Deacon, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Denmark
Baptist Gallwitz, Department of Medicine IV, Eberhard-Karls-University, Tübingen, Germany
Supported by the Wilhelm-Sander-Stiftung (No. 2002.025.1 to JJM), Deutsche Forschungsgemeinschaft (grants Me 2096/2-1, Na 203/6-1 and Ga 386/8-1) and the Deutsche Diabetes Gesellschaft (to JJM)
Correspondence to: Dr. Juris J Meier, Department of Medicine I, St. Josef-Hospital, Ruhr-University of Bochum Gudrunstr. 56 44791 Bochum, Germany. juris.meier@rub.de
Telephone: +49-234-509-2712/-1 Fax: +49-234-509-2309
Received: June 9, 2005
Revised: July 2, 2005
Accepted: August 26, 2005
Published online: March 28, 2006
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 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/m2; no history of autonomic neuropathy) and 8 healthy subjects (2/6, 46 ± 6 years., 28.9 ± 5.3 kg/m2). 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.

Keywords: Gastric inhibitory polypeptide; Gastric acid secretion; Type 2 diabetes; Hyperglycemic clamp; Pentagastrin-stimulated acid secretion