Therapeutic vaccine against DPP4 improves glucose metabolism in mice
| Autor: | Ryuichi Morishita, Futoshi Nakagami, Hitomi Kurinami, Mariana Kiomy Osako, Hideki Tomioka, Yoichi Takami, Zhengda Pang, Hiromi Rakugi, Hironori Nakagami, Munehisa Shimamura, Hiroshi Koriyama |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty endocrine system diseases Dipeptidyl Peptidase 4 T-Lymphocytes Carbohydrate metabolism Diet High-Fat Lymphocyte Activation medicine.disease_cause Diabetes Mellitus Experimental Autoimmunity Mice Insulin resistance Internal medicine Diabetes mellitus MODELOS ANIMAIS DE DOENÇAS medicine Animals Amino Acid Sequence Antigens Dipeptidyl peptidase-4 Vaccines Multidisciplinary business.industry Vaccination nutritional and metabolic diseases Type 2 Diabetes Mellitus medicine.disease Mice Inbred C57BL Disease Models Animal Glucose Treatment Outcome Postprandial Endocrinology Diabetes Mellitus Type 2 PNAS Plus Insulin Resistance Peptides business |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1322009111 |
| Popis: | The increasing prevalence of type 2 diabetes mellitus is associated with a significant economic burden. We developed a dipeptidyl peptidase 4 (DPP4)-targeted immune therapy to increase glucagon-like peptide 1 hormone levels and improve insulin sensitivity for the prevention and treatment of type 2 diabetes mellitus. Immunization with the DPP4 vaccine in C57BL/6J mice successfully increased DPP4 titer, inhibited plasma DPP4 activity, and induced an increase in the plasma glucagon-like peptide 1 level. Moreover, this elevated titer was sustained for 3 mo. In mice fed a high-fat diet, DPP4 vaccination resulted in improved postprandial glucose excursions and insulin sensitivity and, in the diabetic KK-A(y) and db/db mice strains, DPP4 vaccination significantly reduced glucose excursions and increased both plasma insulin and pancreatic insulin content. Importantly, T cells were not activated following challenge with DPP4 itself, which suggests that this vaccine does not induce cell-mediated autoimmunity. Additionally, no significant immune-mediated damage was detected in cells and tissues where DPP4 is expressed. Thus, this DPP4 vaccine may provide a therapeutic alternative for patients with diabetes. |
| Databáze: | OpenAIRE |
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