Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of diabetic nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) may depend on factors other than the quality of diabetes control. Hypertension is an additional factor associated with a high degree of renal involvement in IDDM. One abnormality consistently observed in various tissues of patients with essential hypertension is enhanced activity of the Na+/H+ antiport. In the present study we have therefore studied platelet antiport activity in 41 healthy subjects (control), in 22 patients with untreated essential hypertension (EH), and in 35 normotensive IDDM patients (type 1). Of these patients 17 exhibited signs of diabetic nephropathy (group 1) while 18 had no evidence for renal involvement of IDDM in spite of a duration of IDDM of at least 10 years (group 2). The two IDDM patient groups were undistinguishable with respect to age, body mass index, and arterial blood pressure (group 1, 117.9 +/- 2.4/78.4 +/- 1.5 mmHg; group 2, 113.9 +/- 3.6/76.1 +/- 1.8 mmHg). Antiporter activity was determined from the rate of cell volume changes induced by propionic acid. Platelet Na+/H+ exchange activity averaged 23.43 +/- 0.43 10(-3).s-1 in control subjects and was markedly elevated in EH (28.38 +/- 0.62 10(-3).s-1; P < 0.01). Antiport activity in group 2 patients without nephropathy averaged 24.54 +/- 0.57 10(-3).s-1 and was undistinguishable from the control group. However, platelet Na+/H+ antiport activity was significantly stimulated in group 1 patients with nephropathy as compared to group 2 (26.95 +/- 0.73 10(-3). s-1; P < 0.025). Our results show that renal involvement in IDDM is associated with enhanced activity of the platelet Na+/H+ antiport.
 ...
PMID:Platelet Na+/H+ antiport activity in patients with insulin-dependent diabetes mellitus with and without diabetic nephropathy. 838 10

One of the mechanisms involved in the progression of diabetic nephropathy, the most common cause of end-stage renal failure, is angiogenic phenomenon associated with the increase of angiogenic factors such as vascular endothelial growth factor (VEGF)-A and angiopoietin (Ang)-2, an antagonist of Ang-1. In the present study, we examined the therapeutic efficacy of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid (NM-3), a small molecule isocoumarin with antiangiogenic activity, using diabetic db/db mice, a model of obese type 2 diabetes. Increases in kidney weight, glomerular volume, creatinine clearance, urinary albumin excretion, total mesangial fraction, glomerular type IV collagen, glomerular endothelial area (CD31(+)), and monocyte/macrophage accumulation (F4/80(+)) observed in control db/db mice were significantly suppressed by daily intraperitoneal injection of NM-3 (100 mg/kg, for 8 weeks). Increases in renal expression of VEGF-A, Ang-2, fibrogenic factor transforming growth factor (TGF)-beta1, and chemokine monocyte chemoattractant protein-1 but not tumor necrosis factor-alpha were also inhibited by NM-3 in db/db mice. Furthermore, decreases of nephrin mRNA and protein levels in db/db mice were recovered by NM-3. In addition, treatment of db/db mice with NM-3 did not affect body weight, blood glucose, serum insulin, or food consumption. NM-3 significantly suppressed the increase of VEGF induced by high glucose in cultured podocytes and also suppressed the increase of VEGF and TGF-beta induced by high glucose in cultured mesangial cells. Taken together, these results demonstrate the potential use of NM-3 as a novel therapeutic agent for renal alterations in type 2 diabetes.
 ...
PMID:2-(8-hydroxy-6-methoxy-1-oxo-1h-2-benzopyran-3-yl) propionic acid, an inhibitor of angiogenesis, ameliorates renal alterations in obese type 2 diabetic mice. 1664 77