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.
Keywords: CXCR3; DPP4; GLP1; T(reg); Type 1 diabetes.
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