The intestine

We have already seen that the intestinal tract, including the stomach, is the source of several hormones that regulate intestinal motility and secretions involved in digestion (Chapter 3). The small and large intestines are also the source of hormones that affect metabolism in the rest of the body, especially through an indirect route, because they affect insulin secretion. Glucose given either orally or intravenously will stimulate insulin secretion. It was observed in the 1960s that if the amounts of glucose were chosen so that the same 'excursion' in plasma glucose concentration were achieved, then considerably more insulin was secreted following oral than intravenous glucose. The suggestion was that hormones secreted from the gut in response to glucose ingestion amplified the effect of glucose on the pancreatic P-cell. These hormones have become known as incretins (Fig. 5.12). There are probably several but one of the most important is glucagon-like peptide-1 (GLP-1). This is secreted from cells known as enteroendocrine L-cells scattered amongst the epithelial cells of the intestinal wall. Like several other hormones we have met in this chapter, GLP-1 is a fragment of a larger prohormone, actually proglucagon, the precursor of pancreatic glucagon (Section 5.1.3). Cleavage of proglucagon in the enteroendocrine cells gives rise to two active products, known as GLP-1 and GLP-2. They get their name because they are similar in sequence to (pancreatic) glucagon, although not identical (approximately 50% amino acid identity). GLP-1 has a number of actions that include inhibition of gastrointestinal motility, but in addition it has a specific effect on the pancreatic P-cell, 'amplifying' glucose-stimulated insulin secretion. There are probably other incretins, including gastric inhibitory

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