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

Heparin binding epidermal growth factor (HB-EGF), a new member of the EGF family, is a potent mitogen for smooth muscle cells, fibroblasts, and mesangial cells. To study whether the HB-EGF is involved in the development of diabetic nephropathy, we measured the expression of the HB-EGF gene in the kidney tissues of streptozotocin-induced diabetic rats by Northern blot analysis. The mean kidney weight of diabetic rats without strict blood sugar control was significantly increased as compared to that of the control group. Renal HB-EGF mRNA expression was also increased in diabetic rats without strict blood sugar control at 7 days after induction of diabetes and remained elevated for the entire 3-month study period. Strict insulin treatment abolished the elevation of HB-EGF mRNA expression and kidney growth. As HB-EGF is a mitogen for mesangial cells, our results suggest that HB-EGF may be involved in the development of diabetic nephropathy.
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PMID:Increased expression of heparin binding epidermal growth-factor-like growth factor mRNA in the kidney of streptozotocin-induced diabetic rats. 785 68

Mesangial cells are responsible for the synthesis of mesangial matrix as well as its degradation, which is mediated by a number of proteolytic activities, including metalloproteinases (MMPs). Imbalanced matrix protein metabolism may be responsible for mesangial expansion and glomerulosclerosis in diabetic nephropathy. Heparin prevents this complication. In human and murine mesangial cell cultures, RT-PCR was able to detect mRNA expression for a number of molecules involved in the mesangial extracellular matrix turnover: type IV collagen [alpha 1(IV)COLL], MMP-1, MMP-2, MMP-3, MMP-9 and MMP-10, and the tissue inhibitors TIMP-1 and TIMP-2. The expression of mRNA for alpha 1(IV)COLL and MMP-2/TIMP-2 balance was studied in human cells in the presence of high glucose and heparin. mRNAs for all the studied molecules were expressed at different levels. Interestingly, a shift in the balance of alpha 1(IV)COLL, MMP-2 and TIMP-2 was observed in high glucose, which was partially reversed by heparin supplementation. The new equilibrium was mostly due to the down-regulation of type IV collagen expression, rather than further reduction of potential proteolysis. Our data, while extending the list of potential mediators of mesangial matrix catabolism, highlight a molecular mechanism by which the pathogenesis of diabetic nephropathy may be sustained, and at the same time suggest that heparin may have the potential to correct this abnormality.
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PMID:Effect of glucose and heparin on mesangial alpha 1(IV)COLL and MMP-2/TIMP-2 mRNA expression. 907 22

Inhibitors of angiotensin converting enzyme (ACE inhibitors) have been introduced more than fifteen years ago into the treatment of hypertension, congestive heart failure, myocardial infarction and diabetic nephropathy. The therapeutic success is related to their action in reduction of plasma and tissue angiotensin II concentrations and potentiation of endogenous kinins. They are able to improve myocardium metabolic status, prevent cardiac hypertrophy, limit myocardial infarct size, and thus prevent heart failure. Since 1987 ACE inhibitors are introduced in the clinical practice in our clinic. We introduced the therapy with lisinopril (Lopril), in 70% of patients among 2855 patients that were admitted in Coronary Care Unit in 1997 and 1998. Lisinopril was introduced as soon as the patient was admitted, together with fibrinolitic, Heparin and Aspirin therapy. Since that time we noticed decrease in postinfarction heart failure in comparison to previous years. We recommend permanent therapy with a small doses of ACE inhibitors in patients with heart infarction.
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PMID:[Converting enzyme inhibitors in acute myocardial infarct and heart failure]. 1035 28

Patients with diabetic nephropathy frequently show increased levels of circulating low-density lipoprotein (LDL) and oxidized LDL, which have been reported to be related to the generation of oxygen-free radicals. In the present study, we evaluated the effects of insulin and heparin on the superoxide production of glomeruli, which were isolated from rats with streptozotocin-induced diabetes for one week, one month, and three months, respectively, and the glomeruli were stimulated with native and oxidized LDL. LDL was isolated from normal subjects with normolipidemia, and the superoxide was measured by using a spectrophotometer. The results demonstrated that the poorly controlled diabetic rat glomeruli showed a significantly higher production of superoxide than normal glomeruli under basal status and after stimulation, and this production increased further with the progression of diabetes. Insulin suppressed both the basal and stimulated production of superoxide in diabetic glomeruli, but not in normal glomeruli. Heparin suppressed superoxide production of diabetic glomeruli stimulated by either native or oxidized LDL, and it also partly suppressed superoxide production of normal glomeruli stimulated by oxidized LDL. Our results suggest that glomerular injury in diabetics with hyperlipidemia may be mediated through enhanced generation of oxygen-free radicals, which can be partially attenuated by insulin and heparin.
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PMID:Insulin and heparin suppress superoxide production in diabetic rat glomeruli stimulated with low-density lipoprotein. 1116 97

The authors report a patient with acute anteroseptal myocardial infarction with a giant left ventricular thrombus at the apex. The patient also had nephrotic syndrome due to diabetic nephropathy. Coronary angiography showed 90% stenosis at segment 6 of the left anterior descending coronary artery. Percutaneous transluminal coronary angioplasty and intracoronary stenting were performed on the 30th day, and effective coronary blood flow was obtained. Heparin was injected intravenously for the first 7 days, and warfarin was administered thereafter. The left ventricular thrombus disappeared after 46 days. No evidence of arterial thromboembolism was found during the disappearance of the left ventricular thrombus as determined by echocardiography.
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PMID:A giant left ventricular thrombus in a patient with acute myocardial infarction--a case report. 1143 35

Angiotensin-converting enzyme inhibitors and angiotensin II (AngII) type 1 receptor blockers lower proteinuria and preserve renal function in diabetic nephropathy (DN). The antiproteinuric effects are greater than their blood pressure reduction, involving the sieving properties of the glomerular filter. In DN, glomerular staining for heparan sulfate proteoglycans is decreased. AngII inhibits heparan sulfate synthesis. Also, heparins modulate AngII signaling in glomerular cells, inhibiting aldosterone synthesis and lowering proteinuria in DN. Is the antiproteinuric effect of heparins due to its interference with the renin-angiotensin-aldosterone system? Ten volunteers each with DN and glomerulonephritis and control subjects were examined before and after low-dosage enoxaparin. Renal hemodynamics were determined with (99m)Tc-DTPA and (131)I-hippurate clearance. Glomerular filtration rate (GFR), effective renal plasma flow, mean arterial pressure, and heart rate were measured at baseline and during AngII infusion before and after enoxaparin while on normal salt and salt restriction. Enoxaparin did not lower aldosterone levels. GFR remained stable in all groups. AngII caused a significant decrease in effective renal plasma flow, whereas mean arterial pressure and heart rate increased significantly. Enoxaparin did not influence the AngII-induced changes of renal hemodynamics during normal salt intake or salt restriction. All groups showed identical responses to AngII before and after enoxaparin. In patients with diabetes, enoxaparin caused a significant decrease in proteinuria. It is concluded that the antiproteinuric effect of heparins in DN cannot be explained via interaction with the renin-angiotensin-aldosterone system. The absence of hemodynamic changes combined with reduced proteinuria point to intrinsic alterations in the glomerular filter. The effects were seen only in DN, not in glomerulonephritis.
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PMID:Proteinuria-lowering effect of heparin therapy in diabetic nephropathy without affecting the renin-angiotensin-aldosterone system. 1769 88