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

Authors Gurgel Penaforte-Saboia J, Couri CEB, Vasconcelos Albuquerque N, Silva VLL, Bitar da Cunha Olegario N, Oliveira Fernandes V, Montenegro RM Junior

Received 30 November 2020

Accepted for publication 26 January 2021

Published 10 February 2021 Volume 2021:14 Pages 565—573


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Ming-Hui Zou

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, Brazil

Correspondence: Renan Magalhães Montenegro Junior
Federal University of Ceará, Rua Coronel Nunes de Melo s/n, Fortaleza, 60430-270, Ceará, Brazil
Tel +55 8533668600
Fax +55 85 3366-8619

Abstract: 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

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