Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function

The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its "incretin effect" in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both and studies have demonstrated that GLP-1 mimetics a...

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Vydané v:Frontiers in endocrinology (Lausanne) Ročník 9; s. 672
Hlavní autori: Rowlands, Jordan, Heng, Julian, Newsholme, Philip, Carlessi, Rodrigo
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Switzerland Frontiers Media S.A 23.11.2018
Predmet:
cell function and integrity
diabetes
Endocrinology
GLP-1
metabolism
signaling
metabolism
GLP-1
signaling
cell function and integrity
diabetes
ISSN:1664-2392, 1664-2392
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Abstract The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its "incretin effect" in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both and studies have demonstrated that GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression, and influence neuroprotective pathways. A substantial body of evidence has accumulated with respect to how GLP-1 and its analogs act to restore and maintain normal cellular functions. These findings have prompted several clinical trials which have reported GLP-1 analogs improve cardiac function, restore lung function and reduce mortality in patients with obstructive lung disease, influence blood pressure and lipid storage, and even prevent synaptic loss and neurodegeneration. Mechanistically, GLP-1 elicits its effects via acute elevation in cAMP levels, and subsequent protein kinase(s) activation, pathways well-defined in pancreatic β-cells which stimulate insulin secretion in conjunction with elevated Ca and ATP. More recently, new studies have shed light on additional downstream pathways stimulated by chronic GLP-1 exposure, findings which have direct relevance to our understanding of the potential therapeutic effects of longer lasting analogs recently developed for clinical use. In this review, we provide a comprehensive description of the diverse roles for GLP-1 across multiple tissues, describe downstream pathways stimulated by acute and chronic exposure, and discuss novel pleiotropic applications of GLP-1 mimetics in the treatment of human disease.
AbstractList The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its "incretin effect" in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both and studies have demonstrated that GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression, and influence neuroprotective pathways. A substantial body of evidence has accumulated with respect to how GLP-1 and its analogs act to restore and maintain normal cellular functions. These findings have prompted several clinical trials which have reported GLP-1 analogs improve cardiac function, restore lung function and reduce mortality in patients with obstructive lung disease, influence blood pressure and lipid storage, and even prevent synaptic loss and neurodegeneration. Mechanistically, GLP-1 elicits its effects via acute elevation in cAMP levels, and subsequent protein kinase(s) activation, pathways well-defined in pancreatic β-cells which stimulate insulin secretion in conjunction with elevated Ca and ATP. More recently, new studies have shed light on additional downstream pathways stimulated by chronic GLP-1 exposure, findings which have direct relevance to our understanding of the potential therapeutic effects of longer lasting analogs recently developed for clinical use. In this review, we provide a comprehensive description of the diverse roles for GLP-1 across multiple tissues, describe downstream pathways stimulated by acute and chronic exposure, and discuss novel pleiotropic applications of GLP-1 mimetics in the treatment of human disease.
The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its “incretin effect” in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both in vitro and in vivo studies have demonstrated that GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression, and influence neuroprotective pathways. A substantial body of evidence has accumulated with respect to how GLP-1 and its analogs act to restore and maintain normal cellular functions. These findings have prompted several clinical trials which have reported GLP-1 analogs improve cardiac function, restore lung function and reduce mortality in patients with obstructive lung disease, influence blood pressure and lipid storage, and even prevent synaptic loss and neurodegeneration. Mechanistically, GLP-1 elicits its effects via acute elevation in cAMP levels, and subsequent protein kinase(s) activation, pathways well-defined in pancreatic β-cells which stimulate insulin secretion in conjunction with elevated Ca2+ and ATP. More recently, new studies have shed light on additional downstream pathways stimulated by chronic GLP-1 exposure, findings which have direct relevance to our understanding of the potential therapeutic effects of longer lasting analogs recently developed for clinical use. In this review, we provide a comprehensive description of the diverse roles for GLP-1 across multiple tissues, describe downstream pathways stimulated by acute and chronic exposure, and discuss novel pleiotropic applications of GLP-1 mimetics in the treatment of human disease.
The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its "incretin effect" in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both in vitro and in vivo studies have demonstrated that GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression, and influence neuroprotective pathways. A substantial body of evidence has accumulated with respect to how GLP-1 and its analogs act to restore and maintain normal cellular functions. These findings have prompted several clinical trials which have reported GLP-1 analogs improve cardiac function, restore lung function and reduce mortality in patients with obstructive lung disease, influence blood pressure and lipid storage, and even prevent synaptic loss and neurodegeneration. Mechanistically, GLP-1 elicits its effects via acute elevation in cAMP levels, and subsequent protein kinase(s) activation, pathways well-defined in pancreatic β-cells which stimulate insulin secretion in conjunction with elevated Ca2+ and ATP. More recently, new studies have shed light on additional downstream pathways stimulated by chronic GLP-1 exposure, findings which have direct relevance to our understanding of the potential therapeutic effects of longer lasting analogs recently developed for clinical use. In this review, we provide a comprehensive description of the diverse roles for GLP-1 across multiple tissues, describe downstream pathways stimulated by acute and chronic exposure, and discuss novel pleiotropic applications of GLP-1 mimetics in the treatment of human disease.The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its "incretin effect" in restoring glucose homeostasis in diabetics, however, it is now apparent that it has a broader range of physiological effects in the body. Both in vitro and in vivo studies have demonstrated that GLP-1 mimetics alleviate endoplasmic reticulum stress, regulate autophagy, promote metabolic reprogramming, stimulate anti-inflammatory signaling, alter gene expression, and influence neuroprotective pathways. A substantial body of evidence has accumulated with respect to how GLP-1 and its analogs act to restore and maintain normal cellular functions. These findings have prompted several clinical trials which have reported GLP-1 analogs improve cardiac function, restore lung function and reduce mortality in patients with obstructive lung disease, influence blood pressure and lipid storage, and even prevent synaptic loss and neurodegeneration. Mechanistically, GLP-1 elicits its effects via acute elevation in cAMP levels, and subsequent protein kinase(s) activation, pathways well-defined in pancreatic β-cells which stimulate insulin secretion in conjunction with elevated Ca2+ and ATP. More recently, new studies have shed light on additional downstream pathways stimulated by chronic GLP-1 exposure, findings which have direct relevance to our understanding of the potential therapeutic effects of longer lasting analogs recently developed for clinical use. In this review, we provide a comprehensive description of the diverse roles for GLP-1 across multiple tissues, describe downstream pathways stimulated by acute and chronic exposure, and discuss novel pleiotropic applications of GLP-1 mimetics in the treatment of human disease.
Author Newsholme, Philip
Heng, Julian
Carlessi, Rodrigo
Rowlands, Jordan
AuthorAffiliation School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute , Perth, WA , Australia
AuthorAffiliation_xml – name: School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute , Perth, WA , Australia
Author_xml – sequence: 1
  givenname: Jordan
  surname: Rowlands
  fullname: Rowlands, Jordan
– sequence: 2
  givenname: Julian
  surname: Heng
  fullname: Heng, Julian
– sequence: 3
  givenname: Philip
  surname: Newsholme
  fullname: Newsholme, Philip
– sequence: 4
  givenname: Rodrigo
  surname: Carlessi
  fullname: Carlessi, Rodrigo
BackLink https://www.ncbi.nlm.nih.gov/pubmed/30532733$$D View this record in MEDLINE/PubMed
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Keywords metabolism
GLP-1
signaling
cell function and integrity
diabetes
Language English
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This article was submitted to Cellular Endocrinology, a section of the journal Frontiers in Endocrinology
Reviewed by: Rudy M. Ortiz, University of California, Merced, United States; Carol Huang, University of Calgary, Canada
Edited by: Damien Keating, Flinders University, Australia
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Snippet The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its "incretin effect" in restoring glucose homeostasis in diabetics, however, it is now...
The incretin hormone Glucagon-Like Peptide-1 (GLP-1) is best known for its “incretin effect” in restoring glucose homeostasis in diabetics, however, it is now...
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SubjectTerms cell function and integrity
diabetes
Endocrinology
GLP-1
metabolism
signaling
Title Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function
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