title: Therapeutic vaccine against DPP4 improves glucose metabolism in mice.
abstract: 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.
authors.affiliation: Departments of Geriatric Medicine and Nephrology and Clinical Gene Therapy, Graduate School of Medicine and Division of Vascular Medicine and Epigenetics, United Graduate School of Child Development, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Zhengda
authors.initials: Z
authors.lastname: Pang
authors.forename: Hironori
authors.initials: H
authors.lastname: Nakagami
authors.forename: Mariana K
authors.initials: MK
authors.lastname: Osako
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koriyama
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nakagami
authors.forename: Hideki
authors.initials: H
authors.lastname: Tomioka
authors.forename: Munehisa
authors.initials: M
authors.lastname: Shimamura
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kurinami
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Takami
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D059305:Diet, High-Fat; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination; D014612:Vaccines / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D000941:Antigens; D010455:Peptides; D014612:Vaccines; D018819:Dipeptidyl Peptidase 4; D005947:Glucose