title: Altered crosstalk in the dipeptidyl peptidase-4-incretin-immune system in type 1 diabetes: A hypothesis generating pilot study.
abstract: Both GLP1(7)(-)(36) (via GLP1 receptor) and the dipeptidyl peptidase-4 (DPP4) cleaved form of GLP1 (GLP1(9)(-)(36), independently of GLP1R) may modulate the response of lymphocytes to cytokine stimuli. The incretin axis, CXCR3 (receptor of DPP4 ligand cytokines CXCL9-11) expression on T(reg)s and hematologic parameters were assessed in 34 patients with long standing type 1 diabetes (T1DM) and in 35 healthy controls. Serum DPP4 (sDPP4) activity, plasma total GLP1 and GLP1(7)(-)(36) concentrations were determined. GLP1(9)(-)(36) concentrations were calculated. CXCR3 expression (flow cytometry) was higher on the CD25(-/)(low)Foxp3(+) than on the CD25(+)Foxp3(+) T(reg)s independently from T1DM, suggesting that CD25(-/)(low)Foxp3(+) T(reg)s are possibly waiting for orientational chemotactic stimuli in a "standby mode". The higher sDPP4 activities in T1DM were inversely correlated with GLP1(7)(-)(36) levels and GLP1(9)(-)(36) levels directly with lymphocyte counts in controls. Our results might indicate an altered DPP4-incretin system and altered immunoregulation including a potentially dysfunctional GLP1(9)(-)(36) signaling in T1DM.
authors.affiliation: 2nd Department of Medicine, Semmelweis University, 46 Szentkirályi Street, 1088 Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Zóka
authors.affiliation: 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, 26 Üllői Street, 1085 Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Barna
authors.affiliation: 1st Department of Obstetrics and Gynecology, Semmelweis University, 27 Baross Street, 1085 Budapest, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Hadarits
authors.affiliation: 2nd Department of Medicine, Semmelweis University, 46 Szentkirályi Street, 1088 Budapest, Hungary.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Al-Aissa
authors.affiliation: Molecular Medicine Research Unit, Hungarian Academy of Sciences, 7 Nádor Street, 1051 Budapest, Hungary.
authors.forename: Barna
authors.initials: B
authors.lastname: Wichmann
authors.affiliation: 2nd Department of Medicine, Semmelweis University, 46 Szentkirályi Street, 1088 Budapest, Hungary.
authors.forename: Györgyi
authors.initials: G
authors.lastname: Műzes
authors.affiliation: 2nd Department of Medicine, Semmelweis University, 46 Szentkirályi Street, 1088 Budapest, Hungary.
authors.forename: Anikó
authors.initials: A
authors.lastname: Somogyi
authors.affiliation: 2nd Department of Medicine, Semmelweis University, 46 Szentkirályi Street, 1088 Budapest, Hungary. Electronic address: firneisz.gabor@med.semmelweis-univ.hu.
authors.forename: Gábor
authors.initials: G
authors.lastname: Firneisz
mesh_terms: D000293:Adolescent; D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000378:metabolism*; D004789:Enzyme Activation; D004804:Eosinophils; D005260:Female; D006801:Humans; D054795:Incretins / Q000097:blood / Q000378:metabolism*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D054367:Receptors, CXCR3 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D054795:Incretins; D054367:Receptors, CXCR3; D018819:Dipeptidyl Peptidase 4
keywords: CXCR3; DPP4; GLP1; T(reg); Type 1 diabetes