Incretin Hormone

An Incretin Hormone is a gut-derived metabolic hormone that stimulates insulin secretion from pancreatic beta cells in a glucose-dependent manner following nutrient ingestion.

• AKA: Intestinal Insulinotropic Hormone, Enteroinsular Hormone, Gut Incretin, Incretin.
• Context:
  • It can typically be secreted by Enteroendocrine Cells in intestinal mucosa.
  • It can typically stimulate Insulin Release only when blood glucose levels are elevated.
  • It can typically account for 50-70% of total Postprandial Insulin Secretion.
  • It can typically be released in response to Oral Nutrient Intake.
  • It can typically be rapidly degraded by Dipeptidyl Peptidase-4 (DPP-4).
  • It can typically regulate Blood Glucose Homeostasis through multiple metabolic pathways.
  • It can typically exhibit the Incretin Effect distinguishing oral from intravenous glucose administration.
  • It can typically have Short Biological Half-Life requiring rapid cellular responses.
  • It can typically bind to G-Protein Coupled Receptors on target cells.
  • It can typically activate Adenylate Cyclase increasing cyclic AMP levels.
  • ...
  • It can often inhibit Glucagon Secretion from pancreatic alpha cells.
  • It can often slow Gastric Emptying delaying nutrient absorption.
  • It can often reduce Food Intake through satiety signaling.
  • It can often promote Beta Cell Proliferation and reduce beta cell apoptosis.
  • It can often improve Insulin Sensitivity in peripheral tissues.
  • It can often be stimulated by Macronutrients including glucose, amino acids, and fatty acids.
  • It can often be modulated by Gut Microbiota through short-chain fatty acids.
  • It can often show reduced effectiveness in Type 2 Diabetes patients.
  • ...
  • It can range from being an Active Incretin Hormone to being a Degraded Incretin Fragment, depending on its enzymatic processing state.
  • It can range from being a Fasting Incretin Level to being a Postprandial Incretin Peak, depending on its nutritional timing.
  • It can range from being a Proximal Gut Incretin to being a Distal Gut Incretin, depending on its intestinal origin site.
  • It can range from being a Primary Incretin Hormone to being a Minor Incretin Hormone, depending on its physiological contribution.
  • ...
  • It can be produced by K Cells in duodenum and jejunum (for GIP).
  • It can be produced by L Cells in ileum and colon (for GLP-1).
  • It can interact with FFAR2 and FFAR3 receptors responding to microbial metabolites.
  • It can be part of the Enteroinsular Axis connecting gut and pancreas.
  • It can be targeted by Incretin-Based Therapies for diabetes treatment.
  • It can belong to the Glucagon Peptide Superfamily sharing structural homology.
  • ...
• Example(s):
  • Primary Incretin Hormones, such as:
    • Glucagon-Like Peptide-1 (GLP-1), secreted by intestinal L-cells with potent insulinotropic effects.
    • Glucose-Dependent Insulinotropic Polypeptide (GIP), secreted by intestinal K-cells as the first discovered incretin.
  • Candidate Incretin Hormones, such as:
    • Glucagon-Like Peptide-2 (GLP-2), with primarily intestinotrophic effects but some metabolic actions.
    • Oxyntomodulin, derived from proglucagon with incretin-like activity.
    • Glicentin, another proglucagon-derived peptide with potential incretin function.
  • Species-Specific Incretins, such as:
    • Xenin, identified in certain species with incretin-like properties.
    • Gastrin-Releasing Peptide, showing incretin activity in specific contexts.
  • Incretin-Related Molecules, such as:
    • Active GLP-1 Forms, including GLP-1 (7-36) amide and GLP-1 (7-37).
    • Active GIP Forms, primarily [[GIP (1-42)] with full biological activity.
    • Truncated Incretin Forms, with reduced or altered metabolic effects.
  • ...
• Counter-Example(s):
  • Insulin, which is secreted by pancreatic beta cells rather than intestinal cells and acts in a glucose-independent manner.
  • Glucagon, which increases blood glucose rather than stimulating insulin secretion.
  • Gastrin, which is a gastrointestinal hormone that primarily regulates gastric acid secretion rather than insulin release.
  • Ghrelin, which is a gut hormone that stimulates appetite but lacks direct insulinotropic effects.
  • Cholecystokinin, which regulates digestion and satiety without significant incretin activity.
  • Somatostatin, which inhibits both insulin and glucagon rather than stimulating insulin secretion.
• See: Enteroendocrine Cell, Dipeptidyl Peptidase-4, Metabolic Hormone, Insulin Secretion, Pancreatic Beta Cell, Blood Glucose Regulation, Incretin Effect, Postprandial Metabolism, Gut-Brain Axis, Type 2 Diabetes, Incretin-Based Therapy, GLP-1 Receptor Agonist, DPP-4 Inhibitor, Gastrointestinal Hormone.

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References

2023

• (Wikipedia, 2023) ⇒ https://en.wikipedia.org/wiki/Incretin Retrieved:2023-12-24.
  • Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism.

    Some incretins (GLP-1) also inhibit glucagon release from the alpha cells of the islets of Langerhans. In addition, they slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. The two main candidate peptides that fulfill criteria for an incretin are the intestinal peptides glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP, also known as: glucose-dependent insulinotropic polypeptide). GIP is produced and secreted into the blood circulation by K cells, i.e., single cells located in the mucosa of the upper gastrointestinal tract's duodenum and upper jejunum while GLP1 is produced and secreted into the blood by L cells located in the mucosa of the lower gastrointestinal tracts small and large intestines. Short-chain fatty acids (primarily acetic, propionic, and butyric acids), which microganisms form in the intestines, bind to the FFAR2 and FFAR3 receptors on K cells and L cells to stimulate their respective production and secretion of GIP and GLP-1. Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4) and are members of the glucagon peptide superfamily.

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