Biology of incretins: GLP-1 and GIP - PubMed (original) (raw)

Review

Biology of incretins: GLP-1 and GIP

Laurie L Baggio et al. Gastroenterology. 2007 May.

Abstract

This review focuses on the mechanisms regulating the synthesis, secretion, biological actions, and therapeutic relevance of the incretin peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The published literature was reviewed, with emphasis on recent advances in our understanding of the biology of GIP and GLP-1. GIP and GLP-1 are both secreted within minutes of nutrient ingestion and facilitate the rapid disposal of ingested nutrients. Both peptides share common actions on islet beta-cells acting through structurally distinct yet related receptors. Incretin-receptor activation leads to glucose-dependent insulin secretion, induction of beta-cell proliferation, and enhanced resistance to apoptosis. GIP also promotes energy storage via direct actions on adipose tissue, and enhances bone formation via stimulation of osteoblast proliferation and inhibition of apoptosis. In contrast, GLP-1 exerts glucoregulatory actions via slowing of gastric emptying and glucose-dependent inhibition of glucagon secretion. GLP-1 also promotes satiety and sustained GLP-1-receptor activation is associated with weight loss in both preclinical and clinical studies. The rapid degradation of both GIP and GLP-1 by the enzyme dipeptidyl peptidase-4 has led to the development of degradation-resistant GLP-1-receptor agonists and dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes. These agents decrease hemoglobin A1c (HbA1c) safely without weight gain in subjects with type 2 diabetes. GLP-1 and GIP integrate nutrient-derived signals to control food intake, energy absorption, and assimilation. Recently approved therapeutic agents based on potentiation of incretin action provide new physiologically based approaches for the treatment of type 2 diabetes.

PubMed Disclaimer

Similar articles

• The biology of incretin hormones.
  Drucker DJ. Drucker DJ. Cell Metab. 2006 Mar;3(3):153-65. doi: 10.1016/j.cmet.2006.01.004. Cell Metab. 2006. PMID: 16517403 Review.
• GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice.
  Hansotia T, Drucker DJ. Hansotia T, et al. Regul Pept. 2005 Jun 15;128(2):125-34. doi: 10.1016/j.regpep.2004.07.019. Regul Pept. 2005. PMID: 15780432 Review.
• Two incretin hormones GLP-1 and GIP: comparison of their actions in insulin secretion and β cell preservation.
  Yabe D, Seino Y. Yabe D, et al. Prog Biophys Mol Biol. 2011 Nov;107(2):248-56. doi: 10.1016/j.pbiomolbio.2011.07.010. Epub 2011 Jul 28. Prog Biophys Mol Biol. 2011. PMID: 21820006 Review.
• The entero-insular axis: implications for human metabolism.
  Ranganath LR. Ranganath LR. Clin Chem Lab Med. 2008;46(1):43-56. doi: 10.1515/CCLM.2008.008. Clin Chem Lab Med. 2008. PMID: 18020966 Review.
• Differential importance of glucose-dependent insulinotropic polypeptide vs glucagon-like peptide 1 receptor signaling for beta cell survival in mice.
  Maida A, Hansotia T, Longuet C, Seino Y, Drucker DJ. Maida A, et al. Gastroenterology. 2009 Dec;137(6):2146-57. doi: 10.1053/j.gastro.2009.09.004. Epub 2009 Sep 17. Gastroenterology. 2009. PMID: 19766644

Cited by

• Oxytocin in growth, reproduction, restoration and health.
  Moberg KU. Moberg KU. Compr Psychoneuroendocrinol. 2024 Sep 30;20:100268. doi: 10.1016/j.cpnec.2024.100268. eCollection 2024 Nov. Compr Psychoneuroendocrinol. 2024. PMID: 39435014 Free PMC article. Review.
• Oral delivery of bioencapsulated exendin-4 expressed in chloroplasts lowers blood glucose level in mice and stimulates insulin secretion in beta-TC6 cells.
  Kwon KC, Nityanandam R, New JS, Daniell H. Kwon KC, et al. Plant Biotechnol J. 2013 Jan;11(1):77-86. doi: 10.1111/pbi.12008. Epub 2012 Oct 18. Plant Biotechnol J. 2013. PMID: 23078126 Free PMC article.
• Protein kinase A mediates glucagon-like peptide 1-induced nitric oxide production and muscle microvascular recruitment.
  Dong Z, Chai W, Wang W, Zhao L, Fu Z, Cao W, Liu Z. Dong Z, et al. Am J Physiol Endocrinol Metab. 2013 Jan 15;304(2):E222-8. doi: 10.1152/ajpendo.00473.2012. Epub 2012 Nov 27. Am J Physiol Endocrinol Metab. 2013. PMID: 23193054 Free PMC article.
• Glucagon's Metabolic Action in Health and Disease.
  Zeigerer A, Sekar R, Kleinert M, Nason S, Habegger KM, Müller TD. Zeigerer A, et al. Compr Physiol. 2021 Apr 1;11(2):1759-1783. doi: 10.1002/cphy.c200013. Compr Physiol. 2021. PMID: 33792899 Free PMC article.
• Distal Enteral Feeding Helps Blood Sugar Control in Pancreatectomized Patients.
  Wu JM, Yang CY, Kuo TC, Lai HS, Chiang PY, Hsieh SH, Tien YW. Wu JM, et al. World J Surg. 2015 Nov;39(11):2771-5. doi: 10.1007/s00268-015-3157-7. World J Surg. 2015. PMID: 26202290

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • ClinicalKey
  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database