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Incretin physiology beyond glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide: cholecystokinin and gastrin peptides

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  1. Oral D/L-3-Hydroxybutyrate stimulates cholecystokinin and insulin secretion and slows gastric emptying in healthy males

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  2. Bilio-enteric flow and plasma concentrations of bile acids after gastric bypass and sleeve gastrectomy

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  3. Circadian variations in plasma concentrations of cholecystokinin and gastrin in man

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  4. Increased oral sodium chloride intake in humans amplifies selectively postprandial GLP-1 but not GIP, CCK, and gastrin in plasma

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Gastrin and cholecystokinin (CCK) are homologous hormone systems known to regulate gastric acid secretion, gallbladder emptying, and cell growth in the pancreas and stomach. They are, however, also involved in the development and secretory functions of pancreatic islet cells. For instance, foetal and neonatal islets express significant amounts of gastrin, and human as well as porcine islet cells express the gastrin/CCK-B receptor abundantly. Therefore, exogenous gastrin and CCK peptides stimulate insulin and glucagon secretion in man. Accordingly, endogenous hypergastrinaemia is accompanied by islet cell hyperplasia and increased insulin secretion. Conventionally, the effect of gastrointestinal hormones on insulin secretion (the incretin effect) has been defined and quantified in relation to oral versus intravenous glucose loadings. Under these unphysiological conditions, the release of gastrin and CCK and, hence, their effect on insulin secretion are modest in comparison with the effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1). Consequently, the interest of CCK and gastrin in incretin research has for decades been limited. A few years ago, however, it was suggested that gastrin together with epidermal growth factor or later GLP-1 might stimulate beta cell growth and secretion. Recent studies have shown that the combination of gastrin and GLP-1 actually restores normoglycaemia in diabetic mice. Therefore, a short review of the incretin system in a broader functional context that includes gastrin and CCK peptides may be timely.
Original languageEnglish
JournalActa Physiologica
Volume201
Issue number4
Pages (from-to)405-11
Number of pages7
ISSN1748-1708
DOIs
Publication statusPublished - 2011

    Research areas

  • Animals, Cholecystokinin, Gastric Inhibitory Polypeptide, Gastrins, Glucagon-Like Peptide 1, Humans, Incretins, Peptides, Receptors, Gastrointestinal Hormone

ID: 33199862