neuropeptide-y and Albuminuria

Albuminuria is an independent risk factor for the progression to end-stage kidney failure, cardiovascular morbidity, and premature death. As such, discovering signaling pathways that modulate albuminuria is desirable. Here, we studied the transcriptomes of podocytes, key cells in the prevention of albuminuria, under diabetic conditions. We found that

Topics: Albuminuria; Animals; Arginine; Benzazepines; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Disease Models, Animal; Down-Regulation; Doxorubicin; Humans; Insulin; Kidney Diseases; Kidney Glomerulus; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Neuropeptide Y; Podocytes; Proteomics; Receptors, Neuropeptide Y; Signal Transduction

The Leucine7 to Proline7 (Leu7Pro) polymorphism of the signal peptide of neuropeptide Y (NPY) increases risk for vascular complications in diabetes. Diabetes is associated with low-grade inflammation, which has an important role in the development of atherosclerosis. Currently, we followed diabetes patients to investigate, if the Pro7 allele is associated with the inflammation related to atherosclerosis.. In the 5-year follow-up, the genotyped, pair-matched type 2 diabetes patients (12 with the Pro7 allele and 19 without) were investigated using non-invasive ultrasound based methods to measure the development of atherosclerosis (intima media thickness=IMT) and endothelium-dependent (FMD) and -independent nitrate-mediated (NMD) vasodilatation. The development of diabetic complications was followed annually, and the concentrations of inflammatory markers and NPY in plasma were determined.. Patients with the Pro7 had increased U-albumin/creatinine (p=0.037), E-selectin (p=0.016), fasting insulin (p=0.011) and HOMA index (p=0.013) but decreased serum amyloid P concentrations (p=0.021). Furthermore, men with the Pro7 had increased CRP (p=0.010) and NPY (p=0.026) concentrations. IMT and FMD were similar in all patients, however, NMD decreased more during the follow-up in the patients with the Pro7 (p=0.002). NPY correlated positively with bIMT [r 0.04 (SE 0.02), p=0.007] and E-selectin negatively with FMD [r -0.05 (S.E 0.02), p=0.039].. Diabetes patients with the Pro7 allele display increased levels of inflammatory molecules and NPY in blood, preceding vascular wall thickening and impaired endothelial dilatation, especially in male patients.

Topics: Aged; Albuminuria; Atherosclerosis; Biomarkers; C-Reactive Protein; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; E-Selectin; Female; Finland; Follow-Up Studies; Genetic Predisposition to Disease; Humans; Inflammation Mediators; Insulin Resistance; Linear Models; Logistic Models; Male; Matched-Pair Analysis; Middle Aged; Neuropeptide Y; Phenotype; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Protein Sorting Signals; Risk Assessment; Risk Factors; Serum Amyloid P-Component; Sex Factors; Time Factors; Ultrasonography; Up-Regulation; Vasodilation