A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

Josh Reed, Stephen Bain, Venkateswarlu Kanamarlapudi Institute of Life Science 1, Medical School, Swansea University, Swansea, SA2 8PP, UKCorrespondence: Venkateswarlu Kanamarlapudi Tel +44 1792 295012Email k.venkateswarlu@swansea.ac.ukAbstract: Type 2 diabetes (T2D), which has currently become a gl...

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Autores principales:	Reed J, Bain S, Kanamarlapudi V
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	diabesity glp-1 glp-1r incretin effect insulin and metabolic homeostasis Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/f624396d525142d898d42f027cfbda04
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spelling	oai:doaj.org-article:f624396d525142d898d42f027cfbda042021-12-02T16:24:36ZA Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives1178-7007https://doaj.org/article/f624396d525142d898d42f027cfbda042021-08-01T00:00:00Zhttps://www.dovepress.com/a-review-of-current-trends-with-type-2-diabetes-epidemiology-aetiology-peer-reviewed-fulltext-article-DMSOhttps://doaj.org/toc/1178-7007Josh Reed, Stephen Bain, Venkateswarlu Kanamarlapudi Institute of Life Science 1, Medical School, Swansea University, Swansea, SA2 8PP, UKCorrespondence: Venkateswarlu Kanamarlapudi Tel +44 1792 295012Email k.venkateswarlu@swansea.ac.ukAbstract: Type 2 diabetes (T2D), which has currently become a global pandemic, is a metabolic disease largely characterised by impaired insulin secretion and action. Significant progress has been made in understanding T2D aetiology and pathogenesis, which is discussed in this review. Extrapancreatic pathology is also summarised, which demonstrates the highly multifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsible for augmenting insulin secretion from pancreatic beta-cells during the postprandial period. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a much longer half-life have been developed, which are currently an effective treatment option for T2D by enhancing insulin secretion in patients. Interestingly, there is continual emerging evidence that these therapies alleviate some of the post-diagnosis complications of T2D. Additionally, these therapies have been shown to induce weight loss in patients, suggesting they could be an alternative to bariatric surgery, a procedure associated with numerous complications. Current GLP-1-based therapies all act as orthosteric agonists for the GLP-1 receptor (GLP-1R). Interestingly, it has emerged that GLP-1R also has allosteric binding sites and agonists have been developed for these sites to test their therapeutic potential. Recent studies have also demonstrated the potential of bi- and tri-agonists, which target multiple hormonal receptors including GLP-1R, to more effectively treat T2D. Improved understanding of T2D aetiology/pathogenesis, coupled with the further elucidation of both GLP-1 activity/targets and GLP-1R mechanisms of activation via different agonists, will likely provide better insight into the therapeutic potential of GLP-1-based therapies to treat T2D.Keywords: diabesity, GLP-1, GLP-1R, incretin effect, insulin, metabolic homeostasisReed JBain SKanamarlapudi VDove Medical Pressarticlediabesityglp-1glp-1rincretin effectinsulinand metabolic homeostasisSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 3567-3602 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabesity glp-1 glp-1r incretin effect insulin and metabolic homeostasis Specialties of internal medicine RC581-951
spellingShingle	diabesity glp-1 glp-1r incretin effect insulin and metabolic homeostasis Specialties of internal medicine RC581-951 Reed J Bain S Kanamarlapudi V A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
description	Josh Reed, Stephen Bain, Venkateswarlu Kanamarlapudi Institute of Life Science 1, Medical School, Swansea University, Swansea, SA2 8PP, UKCorrespondence: Venkateswarlu Kanamarlapudi Tel +44 1792 295012Email k.venkateswarlu@swansea.ac.ukAbstract: Type 2 diabetes (T2D), which has currently become a global pandemic, is a metabolic disease largely characterised by impaired insulin secretion and action. Significant progress has been made in understanding T2D aetiology and pathogenesis, which is discussed in this review. Extrapancreatic pathology is also summarised, which demonstrates the highly multifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsible for augmenting insulin secretion from pancreatic beta-cells during the postprandial period. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a much longer half-life have been developed, which are currently an effective treatment option for T2D by enhancing insulin secretion in patients. Interestingly, there is continual emerging evidence that these therapies alleviate some of the post-diagnosis complications of T2D. Additionally, these therapies have been shown to induce weight loss in patients, suggesting they could be an alternative to bariatric surgery, a procedure associated with numerous complications. Current GLP-1-based therapies all act as orthosteric agonists for the GLP-1 receptor (GLP-1R). Interestingly, it has emerged that GLP-1R also has allosteric binding sites and agonists have been developed for these sites to test their therapeutic potential. Recent studies have also demonstrated the potential of bi- and tri-agonists, which target multiple hormonal receptors including GLP-1R, to more effectively treat T2D. Improved understanding of T2D aetiology/pathogenesis, coupled with the further elucidation of both GLP-1 activity/targets and GLP-1R mechanisms of activation via different agonists, will likely provide better insight into the therapeutic potential of GLP-1-based therapies to treat T2D.Keywords: diabesity, GLP-1, GLP-1R, incretin effect, insulin, metabolic homeostasis
format	article
author	Reed J Bain S Kanamarlapudi V
author_facet	Reed J Bain S Kanamarlapudi V
author_sort	Reed J
title	A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
title_short	A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
title_full	A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
title_fullStr	A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
title_full_unstemmed	A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
title_sort	review of current trends with type 2 diabetes epidemiology, aetiology, pathogenesis, treatments and future perspectives
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/f624396d525142d898d42f027cfbda04
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A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

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