Emerging Roles of Dipeptidyl Peptidase-4 Inhibitors in Delaying the Progression of Type 1 Diabetes Mellitus

Jaquellyne Gurgel Penaforte-Saboia,1,2 Carlos Eduardo Barra Couri,3 Natasha Vasconcelos Albuquerque,1,4 Vanessa Lauanna Lima Silva,5 Natália Bitar da Cunha Olegario,1,2 Virgínia Oliveira Fernandes,1,2,4 Renan Magalhães Montenegro Junior1,2,4 1Clinical Research Unit,...

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Autores principales:	Gurgel Penaforte-Saboia J, Couri CEB, Vasconcelos Albuquerque N, Silva VLL, Bitar da Cunha Olegario N, Oliveira Fernandes V, Montenegro RM Junior
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	cd26 type 1 diabetes mellitus autoimmunity autoantibodies therapeutic targets prevention. Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/3a1e029995cf4b5490aa9da89ab191ed
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spelling	oai:doaj.org-article:3a1e029995cf4b5490aa9da89ab191ed2021-12-02T13:30:40ZEmerging Roles of Dipeptidyl Peptidase-4 Inhibitors in Delaying the Progression of Type 1 Diabetes Mellitus1178-7007https://doaj.org/article/3a1e029995cf4b5490aa9da89ab191ed2021-02-01T00:00:00Zhttps://www.dovepress.com/emerging-roles-of-dipeptidyl-peptidase-4-inhibitors-in-delaying-the-pr-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Jaquellyne Gurgel Penaforte-Saboia,1,2 Carlos Eduardo Barra Couri,3 Natasha Vasconcelos Albuquerque,1,4 Vanessa Lauanna Lima Silva,5 Natália Bitar da Cunha Olegario,1,2 Virgínia Oliveira Fernandes,1,2,4 Renan Magalhães Montenegro Junior1,2,4 1Clinical Research Unit, Walter Cantidio University Hospital, Federal University of Ceará, Fortaleza, Brazil; 2Department of Clinical Medicine, Federal University of Ceará, Fortaleza, Brazil; 3Center for Cell-Based Therapy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil; 4Department of Community Health, Federal University of Ceará, Fortaleza, Brazil; 5Department of Clinical Medicine, Hospital and Maternity Dra Zilda Arns Neumann, Fortaleza, BrazilCorrespondence: Renan Magalhães Montenegro JuniorFederal University of Ceará, Rua Coronel Nunes de Melo s/n, Fortaleza, 60430-270, Ceará, BrazilTel +55 8533668600Fax +55 85 3366-8619Email renanmmjr@gmail.comAbstract: Type 1 diabetes mellitus (T1DM) results from the immune cell-mediated destruction of functional pancreatic β-cells. In the presymptomatic period, T1DM is characterized by the presence of two or more autoantibodies against the islet cells in patients without glycemic decompensation. Therapeutic strategies that can modify the autoimmune process could slow the progression of T1DM. Dipeptidyl peptidase-4 (DPP-4) or CD26, a multifunctional serine protease with a dual function (regulatory protease and binding protein), can modulate inflammation and immune cell-mediated β-cell destruction. CD26 is involved in T-cell co-stimulation, migration, memory development, thymic maturation, and emigration patterns. DPP-4 degrades the peptide hormones GLP-1 and GIP. In addition to regulating glucose metabolism, DPP-4 exerts anti-apoptotic, regenerative, and proliferative effects to promote β-cell mass expansion. GLP-1 receptor signaling may regulate murine lymphocyte proliferation and maintenance of peripheral regulatory T-cells. In patients with T1DM, the serum DPP-4 activity is upregulated. Several studies have suggested that the upregulated DPP-4 activity is correlated with T1DM pathophysiology. DPP-4, which is preferentially expressed on the Th1 surface, can promote the polarization of Th1 immunity, a prerequisite for T1DM development. CD26 inhibition can suppress T-cell proliferation and Th1 cytokine production and stimulate tumor growth factor beta-1 (TGF-β 1) secretion, which plays an important role in the regulation of autoimmunity in T1DM. Studies on humans or animal models of T1DM have suggested that DPP-4 inhibitors can improve β-cell function and attenuate autoimmunity in addition to decreasing insulin dependence. This review summarizes the emerging roles of DPP-4 inhibitors in potentially delaying the progression of T1DM.Keywords: CD26, type 1 diabetes mellitus, autoimmunity, autoantibodies, therapeutic targets, preventionGurgel Penaforte-Saboia JCouri CEBVasconcelos Albuquerque NSilva VLLBitar da Cunha Olegario NOliveira Fernandes VMontenegro RM JuniorDove Medical Pressarticlecd26type 1 diabetes mellitusautoimmunityautoantibodiestherapeutic targetsprevention.Specialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 565-573 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cd26 type 1 diabetes mellitus autoimmunity autoantibodies therapeutic targets prevention. Specialties of internal medicine RC581-951
spellingShingle	cd26 type 1 diabetes mellitus autoimmunity autoantibodies therapeutic targets prevention. Specialties of internal medicine RC581-951 Gurgel Penaforte-Saboia J Couri CEB Vasconcelos Albuquerque N Silva VLL Bitar da Cunha Olegario N Oliveira Fernandes V Montenegro RM Junior Emerging Roles of Dipeptidyl Peptidase-4 Inhibitors in Delaying the Progression of Type 1 Diabetes Mellitus
description	Jaquellyne Gurgel Penaforte-Saboia,1,2 Carlos Eduardo Barra Couri,3 Natasha Vasconcelos Albuquerque,1,4 Vanessa Lauanna Lima Silva,5 Natália Bitar da Cunha Olegario,1,2 Virgínia Oliveira Fernandes,1,2,4 Renan Magalhães Montenegro Junior1,2,4 1Clinical Research Unit, Walter Cantidio University Hospital, Federal University of Ceará, Fortaleza, Brazil; 2Department of Clinical Medicine, Federal University of Ceará, Fortaleza, Brazil; 3Center for Cell-Based Therapy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil; 4Department of Community Health, Federal University of Ceará, Fortaleza, Brazil; 5Department of Clinical Medicine, Hospital and Maternity Dra Zilda Arns Neumann, Fortaleza, BrazilCorrespondence: Renan Magalhães Montenegro JuniorFederal University of Ceará, Rua Coronel Nunes de Melo s/n, Fortaleza, 60430-270, Ceará, BrazilTel +55 8533668600Fax +55 85 3366-8619Email renanmmjr@gmail.comAbstract: Type 1 diabetes mellitus (T1DM) results from the immune cell-mediated destruction of functional pancreatic β-cells. In the presymptomatic period, T1DM is characterized by the presence of two or more autoantibodies against the islet cells in patients without glycemic decompensation. Therapeutic strategies that can modify the autoimmune process could slow the progression of T1DM. Dipeptidyl peptidase-4 (DPP-4) or CD26, a multifunctional serine protease with a dual function (regulatory protease and binding protein), can modulate inflammation and immune cell-mediated β-cell destruction. CD26 is involved in T-cell co-stimulation, migration, memory development, thymic maturation, and emigration patterns. DPP-4 degrades the peptide hormones GLP-1 and GIP. In addition to regulating glucose metabolism, DPP-4 exerts anti-apoptotic, regenerative, and proliferative effects to promote β-cell mass expansion. GLP-1 receptor signaling may regulate murine lymphocyte proliferation and maintenance of peripheral regulatory T-cells. In patients with T1DM, the serum DPP-4 activity is upregulated. Several studies have suggested that the upregulated DPP-4 activity is correlated with T1DM pathophysiology. DPP-4, which is preferentially expressed on the Th1 surface, can promote the polarization of Th1 immunity, a prerequisite for T1DM development. CD26 inhibition can suppress T-cell proliferation and Th1 cytokine production and stimulate tumor growth factor beta-1 (TGF-β 1) secretion, which plays an important role in the regulation of autoimmunity in T1DM. Studies on humans or animal models of T1DM have suggested that DPP-4 inhibitors can improve β-cell function and attenuate autoimmunity in addition to decreasing insulin dependence. This review summarizes the emerging roles of DPP-4 inhibitors in potentially delaying the progression of T1DM.Keywords: CD26, type 1 diabetes mellitus, autoimmunity, autoantibodies, therapeutic targets, prevention
format	article
author	Gurgel Penaforte-Saboia J Couri CEB Vasconcelos Albuquerque N Silva VLL Bitar da Cunha Olegario N Oliveira Fernandes V Montenegro RM Junior
author_facet	Gurgel Penaforte-Saboia J Couri CEB Vasconcelos Albuquerque N Silva VLL Bitar da Cunha Olegario N Oliveira Fernandes V Montenegro RM Junior
author_sort	Gurgel Penaforte-Saboia J
title	Emerging Roles of Dipeptidyl Peptidase-4 Inhibitors in Delaying the Progression of Type 1 Diabetes Mellitus
title_short	Emerging Roles of Dipeptidyl Peptidase-4 Inhibitors in Delaying the Progression of Type 1 Diabetes Mellitus
title_full	Emerging Roles of Dipeptidyl Peptidase-4 Inhibitors in Delaying the Progression of Type 1 Diabetes Mellitus
title_fullStr	Emerging Roles of Dipeptidyl Peptidase-4 Inhibitors in Delaying the Progression of Type 1 Diabetes Mellitus
title_full_unstemmed	Emerging Roles of Dipeptidyl Peptidase-4 Inhibitors in Delaying the Progression of Type 1 Diabetes Mellitus
title_sort	emerging roles of dipeptidyl peptidase-4 inhibitors in delaying the progression of type 1 diabetes mellitus
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/3a1e029995cf4b5490aa9da89ab191ed
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Emerging Roles of Dipeptidyl Peptidase-4 Inhibitors in Delaying the Progression of Type 1 Diabetes Mellitus

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