胃抑制多肽对2型糖尿病患者和健康对照者中五肽胃泌素刺激的胃酸分泌的影响。

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

作者信息

Meier Juris J, Nauck Michael A, Kask Bartholomaeus, Holst Jens J, Deacon Carolyn F, Schmidt Wolfgang E, Gallwitz Baptist

机构信息

Department of Medicine I, St. Josef-Hospital, Ruhr-University of Bochum, Gudrunstrasse 56, 44791 Bochum, Germany.

出版信息

World J Gastroenterol. 2006 Mar 28;12(12):1874-80. doi: 10.3748/wjg.v12.i12.1874.

DOI:10.3748/wjg.v12.i12.1874

PMID:16609993

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4087512/

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.

摘要

目的

胃抑制性多肽由肠道K细胞在摄入营养物质后分泌，在人体生理学中作为一种肠促胰岛素激素发挥作用。虽然动物实验表明胃抑制性多肽具有抑制胃分泌的作用，但胃抑制性多肽对人体胃酸分泌的影响仍存在争议。

方法

对8例2型糖尿病患者（2例女性，6例男性，年龄54±10岁，体重指数30.5±2.2kg/m²；无自主神经病变病史）和8例健康受试者（2例女性，6例男性，年龄46±6岁，体重指数28.9±5.3kg/m²），以1μg·kg⁻¹·h⁻¹的输注速率静脉输注五肽胃泌素300分钟。进行240分钟的高血糖钳夹（140mg/dl）。分别在60分钟内给予安慰剂、生理剂量的胃抑制性多肽（1pmol·kg⁻¹·min⁻¹）和药理剂量的胃抑制性多肽（4pmol·kg⁻¹·min⁻¹）。在每个输注期开始时，分别静脉注射安慰剂、胃抑制性多肽20pmol/kg和胃抑制性多肽80pmol/kg的推注剂量。每隔15分钟分析胃容积、酸和氯的分泌量。采集毛细血管和静脉血样以测定血糖和总胃抑制性多肽。采用重复测量方差分析和单因素方差分析进行统计学分析。

结果

2型糖尿病患者和对照组在高血糖钳夹实验期间的血浆葡萄糖浓度无差异。在健康对照受试者和2型糖尿病患者中，低剂量和高剂量输注胃抑制性多肽期间，胃抑制性多肽的稳态血浆水平分别为61±8和79±12pmol/L以及327±35和327±17pmol/L（P=0.23和P=0.99）。五肽胃泌素显著增加胃酸和氯的分泌（P<0.001）。在给予安慰剂或任何剂量胃抑制性多肽的实验期间，胃酸或氯分泌速率无显著差异。2型糖尿病患者和健康对照者胃酸和氯分泌的时间模式相似（分别为P=0.86和P=0.61）。