Gastrointestinal peptides--rôle in pathophysiology and disease

Progress in gut hormone research has considerably increased our knowledge in gastrointestinal physiology. However, this knowledge has not yet helped the understanding of common gastrointestinal diseases. A pathophysiological role of gut hormones has been established only for rare conditions This is because the clinical significance of the gut hormones is difficult to evaluate. Morphological and biochemical methods used in classical endocrinology can rarely be applied to gastrointestinal endocrinology because of the special design of the gut hormone system. Also gut hormones and autonomous nervous system overlap in their function. A defect of one system can be compensated by the other. Since the hormone-producing cells of the gut are stimulated by food ingestion, any functional or organic change of the digestive tract will alter gut hormone response. Accordingly, most changes of gut hormone levels are secondary. In some--apparently rare--instances such secondary changes contribute to the symptomatology of a pathological condition. In other instances gut hormone abnormalities mimic common diseases, thus demonstrating the heterogenecity of these conditions. More specific and reliable methods are needed to prove or to exclude the participation of gastrointestinal peptides in the pathogenesis of gastrointestinal disease. Gut peptides are an important link between nutrient entry and metabolism. This is realized by a hormonal gut factor (incretin) which augments glucose-induced insulin release. GIP is the most thoroughly investigated but not the only incretin. In addition, GIP seems to have direct effects on lipid metabolism. This would explain why fat releases more GIP than glucose. Except in the case of the metabolic hormones insulin and glucagon the therapeutic usefulness of gastrointestinal peptides has not yet been established.