Protective effect of statin therapy on connective tissue growth factor induction by diabetes in vivo and high glucose in vitro.

Transcriptional activity of connective tissue growth factor (CTGF) promoter in transfected HEK293 cells was determined by luciferase assays. Secreted CTGF in cultured human mesangial cells was measured by enzyme-linked immunosorbent assay (ELISA). CTGF in urine and plasma was also measured in 405 subjects with/without type 2 diabetes.

Elevated activity of transcription factor nuclear factor of activated T-cells 5 (NFAT5) and diabetic nephropathy.

The expression of aldose reductase is tightly regulated by the transcription factor tonicity response element binding protein (TonEBP/NFAT5) binding to three osmotic response elements (OREs; OREA, OREB, and OREC) in the gene. The aim was to investigate the contribution of NFAT5 to the pathogenesis of diabetic nephropathy. Peripheral blood mononuclear cells (PBMCs) were isolated from the following subjects: 44 Caucasoid patients with type 1 diabetes, of whom 26 had nephropathy and 18 had no nephropathy after a diabetes duration of 20 years, and 13 normal healthy control subjects.

Glucose transporter polymorphisms are associated with clear-cell renal carcinoma.

Clear-cell renal cell carcinoma (CCRCC) is identified by abundant glycogen-rich cytoplasm, due to the aberrant influx and storage of glucose. The objective was to investigate the frequency of polymorphisms of the facilitative glucose transporter (GLUT1). GLUT1 is a downstream target of Hypoxia-inducible factor (HIF-1alpha), a mediator of hypoxia-controlled angiogenesis.

Association of the p22phox component of NAD(P)H oxidase with susceptibility to diabetic nephropathy in patients with type 1 diabetes.

Objective: Increased production of reactive oxygen species (ROS) in diabetes is thought to play a major role in the pathogenesis of diabetic microvascular complications such as nephropathy and retinopathy. The NAD(P)H oxidase complex is an important source of ROS in the vasculature. The p22 subunit is polymorphic with a C242T variant that changes histidine-72 for a tyrosine in the potential heme binding site, together with a A640G in the 3' untranslated region.

The response of antioxidant genes to hyperglycemia is abnormal in patients with type 1 diabetes and diabetic nephropathy.

Increased flux of glucose through the polyol pathway may cause generation of excess reactive oxygen species (ROS), leading to tissue damage. Abnormalities in expression of enzymes that protect against oxidant damage may accentuate the oxidative injury. The expression of catalase (CAT), CuZn superoxide-dismutase (CuZnSOD), glutathione peroxidase (GPX), and Mn superoxide-dismutase (MnSOD) mRNA was quantified in peripheral blood mononuclear cells-obtained from 26 patients with type 1 diabetes and nephropathy, 15 with no microvascular complications after 20 years' duration of diabetes, and 10 normal healthy control subjects-that were exposed in vitro to hyperglycemia (HG) (31 mmol/l D-glucose).