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)

1. To dissociate the effects on the development of diabetic renal injury of angiotensin converting enzyme (ACE) inhibition per se, and a reduction in systemic blood pressure, we have studied the effects of chronic ramapril treatment in streptozotocin diabetic spontaneously hypertensive rats, with modulation of the hypotensive effect by a high salt diet. 2. Three weeks following uninephrectomy and induction of diabetes with streptozotocin, spontaneously hypertensive rats were allocated to three treatment groups. Groups 1 and 2 received 1% sodium chloride and Group 3 water as drinking solution. Groups 2 and 3 received 0.4 mg/kg per day ramapril in drinking solution over the subsequent 2 month study period. 3. Sodium chloride drinking solution (1%) completely prevented any hypotensive effect of ramapril. Blood pressure was reduced in Group 3 rats over the entire period of study, when compared with Group 2 rats (P less than 0.001). 4. Urinary protein excretion progressively increased in Group 1 and 2 rats, and was significantly reduced (P less than 0.001) in Group 3. After 2 months treatment, urinary protein (expressed as mean and s.e.m.) was 160 +/- 30 mg/day in Group 1, 240 +/- 50 mg/day in Group 2, and 60 +/- 11 mg/day in Group 3. 5. Angiotensin converting enzyme inhibition per se was not associated with a reduced protein excretion in diabetic nephropathy, requiring concomitant control of systemic blood pressure to become renoprotective.
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PMID:High salt diet ameliorates effects of angiotensin converting enzyme inhibition in spontaneously hypertensive streptozotocin diabetic rats. 214 Mar 3

The effects of dietary salt restriction on the renin-angiotensin system, glomerular filtration rate (GFR), renal size, and albuminuria were assessed in streptozotocin diabetic rats. Two series of experiments were performed: one short-term with severe salt restriction and the second long-term with moderate salt restriction. The first studied the effect of a very-low-salt diet for 4 weeks on GFR, renal size, and plasma angiotensin II concentration in diabetic and control rats. Diabetic and control male Sprague-Dawley rats received either a very-low-salt (0.005% NaCl) or a normal-salt (0.4% NaCl) diet. Diabetes was associated with a 49% increase in GFR, a 34% increase in kidney weight, and an 85% reduction in plasma angiotensin II when compared with control rats (P < 0.001). Sodium restriction in diabetic rats reduced GFR, restored plasma angiotensin II to control values, and retarded kidney growth when compared with diabetic rats receiving a normal sodium diet. GFR correlated negatively with plasma angiotensin II (r = -0.65, P < 0.001) and positively with kidney weight (r = 0.66, P < 0.001). In the second experiment, serial measurements of albuminuria and GFR were performed in control, diabetic, and salt-restricted (0.05% NaCl) control and diabetic rats over 24 weeks. Albuminuria showed a continuous rise in the diabetic rats when compared with control rats. Salt restriction attenuated the increase in albuminuria over the whole study period as well as reducing blood pressure and kidney weight in the diabetic rats. In conclusion, sodium restriction was associated with a lower GFR and kidney weight after 4 weeks and reduced levels of albuminuria, kidney weight, and blood pressure after 24 weeks in diabetic rats. Salt restriction may have an important role in the prevention and treatment of diabetic nephropathy.
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PMID:Salt restriction reduces hyperfiltration, renal enlargement, and albuminuria in experimental diabetes. 897 Oct 91

Patients with diabetic nephropathy have an increased risk of coronary heart disease (CHD). Paraoxonase (Pon1) is a high-density lipoprotein- (HDL) associated enzyme that protects low-density lipoprotein from oxidation and also protects against atherosclerosis. We investigated the relationship of serum Pon1 activity, Pon1 Q192R polymorphism and HDL-C level to type 2 diabetes mellitus (DM) in patients on maintenance hemodialysis (HD). DM patients (n = 56, F/M = 17/39, aged 64.5 +/- 7.5 years) and non-DM patients (n = 89, F/M = 28/61, aged 62.7 +/- 8.3 years) under HD were included in this study. Salt-stimulated serum Pon1 activities were measured using paraoxon as a substrate. Pon1 Q192R polymorphism was detected by the mutagenically separated polymerase chain reaction. DM patients on HD had significantly lower HDL-C levels and serum Pon1 activities than non-DM patients on HD (657 +/- 277 vs. 763 +/- 257 IU/l, p < 0.01). The distribution of Pon1 Q 192R genotypes in all subjects did not differ from that predicted from the Hardy-Weinberg equilibrium. Serum Pon1 activities in both DM and non-DM patients on HD were regulated by Pon1 Q192R polymorphism: RR > QR > QQ. However, the reduced Pon1 activities in DM patients on HD were related to DM independent of the Pon1 genotype: reduced Pon1 activity was related to DM in RR carriers. Serum Pon1 activities were positively correlated with HDL-C levels. The association between HDL-C and DM in hemodialyzed patients was independent of Pon1 activity as assessed by an analysis of variance. But the relation between Pon1 activity and DM was modified by HDL-C levels: significantly when HDL-C was below 50 mg/dl, but not significantly when HDL-C was above 50 mg/dl. The results of a logistic regression analysis show that reduced serum Pon1 activities and low HDL-C levels were additively associated with DM. In conclusion, Pon1 status and HDL levels are independently associated with DM in patients on hemodialysis and may contribute to the increased risk of CHD in diabetic nephropathy.
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PMID:Paraoxonase (Pon1) Q192R polymorphism and serum Pon1 activity in diabetic patients on maintenance hemodialysis. 1457 40

Injury to podocytes is considered a major contributor to diabetic kidney disease: their loss causes proteinuria and progressive glomerulosclerosis. Podocyte depletion may result from improper calcium handling due to abnormal activation of the calcium permeant TRPC (Transient Receptor Potential Canonical) channels. Angiotensin II (Ang II) levels are found to be elevated in diabetes; furthermore, it was reported that Ang II causes activation of TRPC6 in podocytes. We hypothesized here that Ang II-mediated calcium influx is aggravated in the podocytes under the conditions of type 1 diabetic nephropathy (DN). Diabetes was induced in the Dahl Salt-Sensitive rats by an injection of streptozotocin (STZ-SS). Eleven weeks post treatment was sufficient for the animals to develop hyperglycemia, excessive urination, weight loss, microalbuminuria, nephrinuria and display renal histological lesions typical for patients with DN. Patch-clamp electrophysiology performed on podocytes of the freshly isolated glomeruli showed enhanced basal TRPC channel activity in the STZ-SS rats, and increased response to Ang II; total calcium influx triggered by Ang II application was also augmented in podocytes of these rats. Our studies have a strong potential for advancing the understanding of TRPC-mediated effects on podocytopenia in DN initiation.
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PMID:Podocyte injury in diabetic nephropathy: implications of angiotensin II-dependent activation of TRPC channels. 2665 1

Worldwide, the number of patients with diabetes is increasing. Adults with diabetes have a two- to threefold increased risk of heart attack and stroke, and diabetic nephropathy is a leading cause of end-stage renal failure. Salt sensitivity of blood pressure is reported to be elevated in patients with diabetes. Hyperinsulinemia, hyperglycemia, and an activated sympathetic nervous system play key roles in the genesis of salt-sensitive blood pressure in individuals who are obese and/or have type 2 diabetes. In this review, I summarize previous research performed to improve our understanding of the relationship between salt and hypertension in diabetic patients.
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PMID:Salt and hypertension in diabetes. 3060 18