**2. Physiological role of the duodenum**

The duodenum is a horseshoe-shaped structure and the first and shortest segment of the small intestine. It is a place of important enzymatic release and where the gastric secretions, bile, and different digestive enzymes from the gallbladder and pancreatic gland merge together. These features make the duodenum play a major role in the regulation of digestion, absorption of nutrients, and gastrointestinal tract motility [5]. One of the main functions is to alkalinize the lumen secretions thus preventing mucosal damage [6, 7]. The duodenum has the luminal capacity to sense the acidic environment generated by the gastric secretions and responds with different coordinated mechanisms that include the efflux of bicarbonate (HCO3-) to stabilize the pH, an increased mucus production by goblet cells and Brunner glands, neuronal activation, and an improvement in the ON-mediated vasodilation consequently enhancing blood flow. The duodenum is also involved in the absorption of calcium and iron [8, 9]. It is the primary site for calcium active transport mediated by vitamin D and absorbs practically all iron from both, heme and nonheme sources being a key element in iron homeostasis and cellular proliferation. This segment of the small bowel is the first site of interaction between the food products and the biliary and pancreatic secretions where the initial steps regarding digestion, hydrolysis, and absorption take place [10]. Proteins, whose digestion starts in the stomach, are finally cleaved and, most of them, absorbed in the duodenum. This process is favored by the pancreatic zymogen trypsinogen, which is converted into trypsin by the duodenal endopeptidase and activates all the other pancreatic zymogens that mediate proteolysis. Lipids on the other hand, after reaching the duodenum, stimulate the secretion of cholecystokinin (CCK), which encourages the release of the pancreatic lipase that conducts their hydrolysis. Moreover, the duodenum produces a variety of gastrointestinal hormones that also play a fundamental role in the digestion and absorption of nutrients [5]. Secretin comes from the S cells in the duodenum and proximal jejunum, and it is released in response to the acidic environment generated by the gastric fluids in the duodenal lumen. It inhibits gastric secretions and emptying, increases the production of mucus and, along with CCK, it stimulates the pancreatic secretion of water and HCO3-. Motilin is another peptide released periodically by the Mo cells and during the fasting period which stimulates the gastric and small intestine motility enabling the movement of food into the large intestine (phase III of the migrating motor complex). These hormone levels vary according to the food consumed decreasing after the ingestion of fat and glucose thus slowing the upper GI tract. The gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are incretins synthesized and secreted by enteroendocrine cells of the small intestine that stimulate insulin secretion from beta-pancreatic cells in a glucose-dependent mechanism. This involvement in the regulation of insulin concentrations makes the inadequate function of these endocrine peptides and reduced circulating levels to be linked to the development of

type 2 diabetes. Somatostatin, on the other hand, displays mainly neuroendocrine inhibitory effects in multiple systems and is produced in different locations, among them, in enteric neural cells and D cells in the duodenum. It is stimulated by the ingestion of proteins and fat, and it reduces the secretion of water and electrolytes, the absorption of amino acids, the gallbladder emptying and CCK production, and the release of insulin resulting in diabetes.

