Secretin

Also known as: SCT, P09683

**Mechanism of Action** Secretin (SCT; gene ID P09683) is a 27-amino-acid peptide hormone primarily secreted by S cells of the duodenum in response to gastric acid. Its canonical mechanism involves binding to the secretin receptor (SCTR), a class B G-protein-coupled receptor, which activates adenylate cyclase and increases intracellular cyclic AMP. This signaling cascade stimulates pancreatic ductal cells to secrete bicarbonate-rich fluid, neutralizing duodenal pH. Additionally, secretin modulates central and peripheral pathways regulating food intake (via vagal afferents and hypothalamic nuclei) and water homeostasis (through renal and osmoregulatory effects). **Key Research Findings** Experimental studies have elucidated secretin’s role beyond gastrointestinal physiology. In the central nervous system, secretin and its receptor are expressed in hypothalamic regions controlling appetite and energy balance; animal models show that central secretin administration reduces food intake and body weight. Research also indicates secretin influences water homeostasis by modulating aquaporin expression in renal collecting ducts and vasopressin release. Despite these findings, clinical translation remains limited, with most data derived from preclinical models. The peptide’s therapeutic potential in metabolic disorders and fluid balance disturbances is under investigation, but no approved clinical applications exist. **Clinical Relevance** Secretin is currently classified as experimental, with no established therapeutic indications. Historical use in diagnostic pancreatic function testing has been largely replaced by non-invasive methods. Ongoing research explores its utility in conditions such as obesity, diabetes, and autism spectrum disorder (based on early, inconclusive trials). However, robust clinical evidence is lacking, and safety profiles in chronic use remain uncharacterized. For research purposes only — not medical advice.

Key data

Mechanism of action

Hormone involved in different processes, such as regulation of the pH of the duodenal content, food intake and water homeostasis (PubMed:25332973). Exerts its biological effects by binding to secretin receptor (SCTR), a G protein-coupled receptor expressed in the basolateral domain of several cells (PubMed:25332973, PubMed:33008599, PubMed:32811827). Acts as a key gastrointestinal hormone by regulating the pH of the duodenal content (By similarity). Secreted by S cells of the duodenum in the crypts of Lieberkuehn and regulates the pH of the duodenum by (1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and (2) stimulating the production of bicarbonate (NaHCO(3)) from the ductal cells of the pancreas (By similarity). Production of bicarbonate is essential to neutralize the pH and ensure no damage is done to the small intestine by the gastric acid (By similarity). In addition to regulating the pH of the duodenal content, plays a central role in diet induced thermogenesis: acts as a non-sympathetic brown fat (BAT) activator mediating prandial thermogenesis, which consequentially induces satiation (Probable). Mechanistically, secretin released by the gut after a meal binds to secretin receptor (SCTR) in brown adipocytes, activating brown fat thermogenesis by stimulating lipolysis, which is sensed in the brain and promotes satiation (By similarity). Also able to stimulate lipolysis in white adipocytes (By similarity). Also plays an important role in cellular osmoregulation: released into the systemic circulation in response to hyperosmolality and acts at different levels in the hypothalamus, pituitary and kidney to regulate water homeostasis (By similarity). Also plays a role in the central nervous system, possibly by acting as a neuropeptide hormone: required for hippocampal synaptic function and neural progenitor cells maintenance (By similarity)

Research & studies

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