Glucagon-like peptide-1

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GLP-1 and diabetes

Glucagon-like peptide-1 (GLP-1) is a neuropeptide and an incretin derived from the transcription product of the proglucagon gene. The major source of GLP-1 in the periphery is the intestinal L cell that secretes GLP-1 as a gut hormone; the major source in the brain is the nucleus of the solitary tract, which is the source of a widely distributed set of GLP-1 projection neurons.[1] The biologically active forms of GLP-1 are: GLP-1-(7-37) and GLP-1-(7-36)NH2. Those peptides result from selective cleavage of the proglucagon molecule.

GLP-1 secretion by ileal L cells is dependent on the presence of nutrients in the lumen of the small intestine. The secretagogues (agents that cause or stimulate secretion) of this hormone include major nutrients like carbohydrate, protein and lipid. Once in the circulation, GLP-1 has a half-life of less than 2 minutes, due to rapid degradation by the enzyme dipeptidyl peptidase-4. It is a potent antihyperglycemic hormone, inducing glucose-dependent stimulation of insulin secretion while suppressing glucagon secretion. Such glucose-dependent action is particularly attractive because, when the plasma glucose concentration is in the normal fasting range, GLP-1 no longer stimulates insulin to cause hypoglycemia. GLP-1 appears to restore the glucose sensitivity of pancreatic β-cells, with the mechanism possibly involving the increased expression of GLUT2 and glucokinase. GLP-1 is also known to inhibit pancreatic β-cell apoptosis and stimulate the proliferation and differentiation of insulin-secreting β-cells. In addition, GLP-1 inhibits gastric secretion and motility. This delays and protracts carbohydrate absorption and contributes to a satiating effect.

Physiological functions[edit]

Visceral functions[edit]

GLP-1 possesses several physiological properties that make it (and its functional analogs) a subject of intensive investigation as a potential treatment of diabetes mellitus.[2][3][4] The known peripheral functions of GLP-1 include:

  • inhibits acid secretion and gastric emptying in the stomach.
  • promotes insulin sensitivity.
  • decreases glucagon secretion from the pancreas via GPCR binding

As evidence of the physiological role of GLP-1 in post-prandial insulin secretion, it has been shown that an oral dose of glucose triggers a much higher peak in plasma insulin concentration compared to an intravenous dose. Obese patients undergoing gastric bypass showed marked metabolic adaptations, resulting in frequent diabetes remission 1 year later. When the confounding of calorie restriction is factored out, β-cell function improves rapidly, very possibly under the influence of enhanced GLP-1 responsiveness.[6] Outside of its function as an insulin secretagogue, GLP-1 seems also to play a role in bone physiology. Researchers evidenced a massive reduction in bone strength in GLP-1 receptor knockout mice mainly due to a poor bone quality.[7]

Insulin release pathways (including GLP-1-induced signaling).

CNS functions[edit]

The primary central nervous system functions of GLP-1 which are known include:[1]

  • decreases the hedonic value (pleasure) of food
  • decreases the motivation (reward) to eat
  • decreases quantity and frequency of food consumption
  • decreases general levels of motor activity

See also[edit]


  1. ^ a b Skibicka KP (2013). "The central GLP-1: implications for food and drug reward". Front Neurosci 7: 181. doi:10.3389/fnins.2013.00181. PMC 3796262. PMID 24133407. Much has been learned about the anatomical, neurochemical, and functional suppressive effects of GLP-1 or its analogs on food intake; GLP-1's ability to suppress food reward behavior is a new concept. ... The collective value of these findings is not only in offering support to the hypothesis that mesolimbic GLP-1 has a specific role in reward behavior but also in emphasizing the neuroanatomical separation of the reward and visceral illness mechanisms of GLP-1. 
    "Figure 1: Effect of GLP-1 on food intake and associated behaviors is neuroanatomicaly distributed"
  2. ^ "Diabetes and Intestinal Incretin Hormones: A New Therapeutic Paradigm" at (slide 36)
  3. ^ Toft-Nielsen MB, Madsbad S, Holst JJ (August 2001). "Determinants of the effectiveness of glucagon-like peptide-1 in type 2 diabetes". The Journal of Clinical Endocrinology and Metabolism 86 (8): 3853–60. doi:10.1210/jcem.86.8.7743. PMID 11502823. 
  4. ^ Meier JJ, Weyhe D, Michaely M, et al. (March 2004). "Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes". Critical Care Medicine 32 (3): 848–51. doi:10.1097/01.CCM.0000114811.60629.B5. PMID 15090972. 
  5. ^ Presswala L, Shubrook J (April 2015). "What to do after basal insulin: 3 Tx strategies for type 2 diabetes". The Journal of family practice 64 (4): 214–20. PMID 25973447. 
  6. ^ Nannipieri M, Baldi S, Mari A, et al. (November 2013). "Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones". The Journal of Clinical Endocrinology and Metabolism 98 (11): 4391–9. doi:10.1210/jc.2013-2538. PMID 24057293. 
  7. ^ Mabilleau G, Mieczkowska A, Irwin N, Flatt PR, Chappard D (October 2013). "Optimal bone mechanical and material properties require a functional glucagon-like peptide-1 receptor". The Journal of Endocrinology 219 (1): 59–68. doi:10.1530/JOE-13-0146. PMID 23911987. 

External links[edit]

American diabetes association:link-