DPP-4 Inhibition Leads to Decreased Pancreatic Inflammatory Profile and Increased Frequency of Regulatory T Cells in Experimental Type 1 Diabetes

Author(s)

Davanso, Mariana Rodrigues ^{[1, 2]} ; Caliari-Oliveira, Carolina ^[3] ; Barra Couri, Carlos Eduardo ^[4] ; Covas, Dimas Tadeu ^{[4, 2]} ; de Oliveira Leal, Angela Merice ^[5] ; Voltarelli, Julio Cesar ^{[4, 2]} ; Ribeiro Malmegrim, Kelen Cristina ^{[6, 2]} ; Ueda Yaochite, Juliana Navarro ^[7]

Affiliation

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Ctr Terapia Celular, Ctr Reg Hemoterapia, Hosp Clin, Rua Tenente Catao Roxo 2501, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Supera Innovat Technol Pk, Situ Cell Therapy, Av Dra Nadir Aguiar 1805, Predio 2, Sala 313, BR-14056680 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Clin Med, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[5] Univ Fed Sao Carlos, Dept Med, Rodovia Washington Luis Km 235, BR-13565905 Sao Carlos, SP - Brazil

^[6] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[7] Univ Fed Ceara, Fac Farm Odontol & Enfermagem, Dept Anal Clin & Toxicol, Rua Alexandre Barauna 949, BR-60430160 Fortaleza, Ceara - Brazil

• Document type: Journal article
• Source: Inflammation; v. 42, n. 2, p. 449-462, APR 2019.
• Web of Science Citations: 0

Abstract

Sitagliptin is a dipeptidyl peptidase-4 inhibitor (iDPP-4), which has been used for type 2 diabetes treatment. Recently, iDPP-4 has been described as a promising treatment of type 1 diabetes (T1D) but is still necessary to evaluate immune effects of sitagliptin. C57BL/6 mice were induced by multiple low doses of streptozotocin. Diabetes incidence, insulin, glucagon, glucagon-like peptide-1 (GLP-1) serum levels, and inflammatory cytokine levels were quantified in pancreas homogenate after 30 and 90days of treatment. In addition, frequencies of inflammatory and regulatory T cell subsets were determined in the spleen and in the pancreatic lymph nodes. iDPP-4 decreased blood glucose level while increased GLP-1 and insulin levels. After long-term treatment, treated diabetic mice presented decreased frequency of CD4(+)CD26(+) T cells and increased percentage of CD4(+)CD25(hi)Foxp3(+) T cells in the spleen. Besides, pancreatic lymph nodes from diabetic mice treated with iDPP-4 presented lower percentage of CD11b(+) cells and decreased levels of inflammatory cytokines in the pancreas. Treatment of type 1 diabetic mice with iDPP-4 improved metabolic control, decreased inflammatory profile in the pancreatic microenvironment, and increased systemic regulatory T cell frequency. Therefore, we suggest the long-term use of sitagliptin as a feasible and effective therapy for T1D. (AU)

• FAPESP's process: 08/57877-3 - National Institute of Science and Technology in Cell Therapy
• Grantee: Roberto Passetto Falcão
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/02074-3 - Therapeutic potential of DPP-4 inhibitor and mesenchymal stromal cells administration in experimental streptozotocin-induced type 1 diabetes mellitus
• Grantee: Mariana Rodrigues Davanso
• Support Opportunities: Scholarships in Brazil - Master