Figure 1 compares the amino acid sequences of secretin (green), vasoactive intestinal peptide (VIP) (blue), and GIP (purple). They are all members of the secretin family; see Table 1. Unlike most other peptide hormones, only one form of secretin is known. Secretin has only 27 amino acids. The entire molecule of 27 amino acids is required for full biological activity. Secretin is localized to the upper duodenal and jejunal S cells. VIP is a peptide that has 28 amino acid residues and is widely expressed in the central and peripheral nervous systems and also in the digestive tract. GIP (purple), also known as glucose-dependent-insulinotropic polypeptide, has 42 amino acids. Ten of VIP’s 28 amino acids (gold) are identical to secretin and are colored gold. Four of its 28 amino acids are identical to GIP and are colored gold. Secretin has only 7 of its 28 amino acids identical to GIP. When VIP and GIP amino acids are identical, they are also colored gold. These matches may reflect evolutionary changes in the order of amino acids.
Fig1. Amino acid sequence comparison of the secretin peptide hormone family. These include secretin (colored green), vasoactive intestinal peptide (VIP; colored blue), and gastrointestinal inhibitory peptide (GIP; colored purple). The three peptides are aligned on the basis of each of the NH2-terminus residue being assigned #1. Each of the 27 amino acid residues of secretin was separately compared with the first 27 residues of VIP and GIP; all amino acid matches between the three peptide hormones were colored gold.
Table1. Gastrointestinal Hormone Families a
Within the GI tract, secretin is found in the S cells of the duodenum and jejunum. Secretin secretion is stimulated by unknown mechanisms when the acidity of the duodenal contents falls below pH ~4.5. The principal biological response of secretin is to stimulate the secretion of bicarbonate and water by the acinar cells of the pancreas. This response is stimulated by ligand occupancy of the secretin receptor, which is located on the outer cell membrane of the pancreatic acinar cells. The human secretin receptor has been cloned and found to be a 419 amino acid peptide (47,900 Da). It belongs to the family of G protein-coupled receptors. Stimulation of adenylate cyclase leads to the secretion of bicarbonate and H2O.
Vasoactive intestinal peptide (VIP) is a 28 amino acid peptide secreted by the small intestine, pancreas, and by the suprachiasmatic region of the hypothalamus in the brain. VIP functions as a neurotransmitter from the esophagus to the rectum and also in the salivary gland. VIP promotes smooth muscle relaxation in the trachea, esophageal sphincter, and the stomach. Gastric inhibitory peptide (GIP) is also known as the glucose-dependent insulinotropic peptide. GIP can induce insulin secretion, which is stimulated primarily by the presence of hyper osmolarity of glucose in the duodenum. GIP is biosynthesized largely by K cells present in the small intestine. K-cells and L-cells secrete respectively the incretins, gastric inhibitory peptide and glucagon-like peptide-1. GIP is released into the circulatory system from the duodenum and jejunum following a mixed meal. Receptors for GIP have been identified in selected regions of the GI tract as well as the brain.
GIP, which is a member of the secretin peptide, shares a high sequence homology with both glucagon (15 amino acids identical) and secretin (6 amino acids identical). Little information is available concerning the mechanisms by which GIP elicits biological responses. Two categories of biological responses are known: (i) inhibition of gastric acid secretion and gastric motility and (ii) potentiation of pancreatic insulin secretion after oral as opposed to intravenous glucose administration.
