Monocyte dipeptidyl peptidase 4 activity is associated with urinary albumin excretion in type 2 diabetes.
L’essentiel
Previous reports have suggested the involvement of pro-inflammatory genes in monocytes and dipeptidyl peptidase 4 (DPP4) in the pathogenesis of diabetic kidney disease (DKD); however, whether DPP4 in monocytes is associated with renal parameters remains unclear. We conducted a cross-sectional study of 64 patients with type 2 diabetes mellitus (T2DM) not taking incretin-based medications and 50 healthy controls not taking any medication and without cardiovascular risk factors. Peripheral blood monocytes were isolated from the participants, cultured, and stimulated with vehicle or lipopolysaccharide (LPS). After cell harvesting, data regarding DPP4 and pro-inflammatory genes in monocytes were investigated by quantitative real-time polymerase chain reaction and DPP4 activity assay. We evaluated renal parameters based on the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). DPP4 gene expression and DPP4 activity in unstimulated monocytes were elevated in patients with T2DM compared with healthy controls. In the T2DM group, DPP4 gene expression in LPS-stimulated monocytes, but not in unstimulated monocytes, was significantly and positively correlated with UACR and the expression of LPS-stimulated pro-inflammatory genes, but not with eGFR. Furthermore, DPP4 activity in both unstimulated and LPS-stimulated monocytes in the T2DM group was significantly and positively correlated with UACR and the expression of LPS-stimulated pro-inflammatory genes but not with eGFR. The findings suggested that monocyte DPP4 activity is associated with urinary albumin excretion in patients with T2DM, with or without LPS stimulation. Monocytes may serve as a cellular link between DPP4 and DKD.
Synthèse détaillée
Résumé original
Previous reports have suggested the involvement of pro-inflammatory genes in monocytes and dipeptidyl peptidase 4 (DPP4) in the pathogenesis of diabetic kidney disease (DKD); however, whether DPP4 in monocytes is associated with renal parameters remains unclear. We conducted a cross-sectional study of 64 patients with type 2 diabetes mellitus (T2DM) not taking incretin-based medications and 50 healthy controls not taking any medication and without cardiovascular risk factors. Peripheral blood monocytes were isolated from the participants, cultured, and stimulated with vehicle or lipopolysaccharide (LPS). After cell harvesting, data regarding DPP4 and pro-inflammatory genes in monocytes were investigated by quantitative real-time polymerase chain reaction and DPP4 activity assay. We evaluated renal parameters based on the urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). DPP4 gene expression and DPP4 activity in unstimulated monocytes were elevated in patients with T2DM compared with healthy controls. In the T2DM group, DPP4 gene expression in LPS-stimulated monocytes, but not in unstimulated monocytes, was significantly and positively correlated with UACR and the expression of LPS-stimulated pro-inflammatory genes, but not with eGFR. Furthermore, DPP4 activity in both unstimulated and LPS-stimulated monocytes in the T2DM group was significantly and positively correlated with UACR and the expression of LPS-stimulated pro-inflammatory genes but not with eGFR. The findings suggested that monocyte DPP4 activity is associated with urinary albumin excretion in patients with T2DM, with or without LPS stimulation. Monocytes may serve as a cellular link between DPP4 and DKD.