The role of the stomach in the control of appetite and the secretion of satiation peptides

Abstract

It is widely accepted that gastric parameters such as gastric distention provide a direct negative feedback signal to inhibit eating; moreover, gastric and intestinal signals have been reported to synergize to promote satiation. However, there are few human data exploring the potential interaction effects of gastric and intestinal signals in the short-term control of appetite and the secretion of satiation peptides. We performed experiments in healthy subjects receiving either a rapid intragastric load or a continuous intraduodenal infusion of glucose or a mixed liquid meal. Intraduodenal infusions (3 kcal/min) were at rates comparable with the duodenal delivery of these nutrients under physiological conditions. Intraduodenal infusions of glucose elicited only weak effects on appetite and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). In contrast, identical amounts of glucose delivered intragastrically markedly suppressed appetite (P Ͻ 0.05) paralleled by greatly increased plasma levels of GLP-1 and PYY (Յ3-fold, P Ͻ 0.05). Administration of the mixed liquid meal showed a comparable phenomenon. In contrast to GLP-1 and PYY, plasma ghrelin was suppressed to a similar degree with both intragastric and intraduodenal nutrients. Our data confirm that the stomach is an important element in the short-term control of appetite and suggest that gastric and intestinal signals interact to mediate early fullness and satiation potentially by increased GLP-1 and PYY secretions. small intestine; humans; glucagon-like peptide-1; gut; interactions EATING IS ORGANIZED INTO DISCRETE MEALS and determined by meal size and meal frequency. Multiple regulatory pathways seem to promote or inhibit eating and thus regulate energy balance. Gastrointestinal (GI) satiation signals such as cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), or peptide YY (PYY) as examples are secreted from the small and large intestine in response to food ingestion and signal to the brain via neural or endocrine pathways to inhibit eating (8). Their plasma levels are low in the fasting state and rise during a meal, which is consistent with the satiating effect observed when peripherally infused in rats and humans (1,19,26). In contrast, the peptide ghrelin is secreted from the stomach during fasting and plasma level fall shortly after meals consistent with a hunger-inducing action observed in rats and humans (47,53).Gastric parameters such as stomach distention are another important source of negative feedback (37). Feelings of hunger and satiety have long been associated with gastric motor and sensory functions, and more importantly, gastric and intestinal signals have been reported to interact (14,18,42). We and other groups could show that in humans oral preloads combined with (exogenously administered or endogenously stimulated) CCK or GLP-1 synergistically increase satiation and reduce food intake (9, 29, 33). Furthermore, Feinle et al. (12) demonstrated that sensory responses to gastric distension are altered by duodenal inf...

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