Open Access Articles- Top Results for Glucagon-like peptide-1

Glucagon-like peptide-1

Glucagon-like peptide-1 (GLP-1) is an incretin derived from the transcription product of the proglucagon gene. The major source of GLP-1 in the body is the intestinal L cell that secretes GLP-1 as a gut hormone. 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

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

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.[5]

Outside of its function as an insulin secretagogue, GLP-1 seems also to play a role in bone physiology. Researchers at Universities of Angers and Ulster evidenced a massive reduction in bone strength in GLP-1 receptor knockout mice mainly due to a poor bone quality.[6]

See also


  1. ^ "Diabetes and Intestinal Incretin Hormones: A New Therapeutic Paradigm" at (slide 36)
  2. ^ 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. PMID 11502823. doi:10.1210/jcem.86.8.7743. 
  3. ^ 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. PMID 15090972. doi:10.1097/01.CCM.0000114811.60629.B5. 
  4. ^ 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. 
  5. ^ 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. PMID 24057293. doi:10.1210/jc.2013-2538. 
  6. ^ 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. PMID 23911987. doi:10.1530/JOE-13-0146. 

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