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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal hypertrophy and hyperfiltration are early manifestations of human and experimental diabetes that may contribute to the late development of diabetic nephropathy. The biochemical events resulting in kidney growth in the diabetic state are completely unknown. Since growth of various tissues is accompanied by increased formation of polyamines, we studied whether polyamines were involved in the growth of the kidney observed in diabetic rats. This was done by measuring the activity of the rate-limiting enzyme in the polyamine pathway (ornithine decarboxylase; ODC) in kidneys from control, diabetic and insulin-treated diabetic animals. The ODC activity in the kidney was increased in the diabetic animals with a maximal rise 24 h after diabetes induction (6-fold, P less than 0.01); the activity thereafter declined. However, on day 14 the activity was still significantly elevated (2.5-fold, P less than 0.05). In insulin-treated diabetic animals the kidney ODC activity was only increased 3-fold (P less than 0.05) after 24 h, and for the rest of the study period the activity was about 1.8-fold higher than in control rats. After 14 days the kidneys from diabetic rats were significantly larger than kidneys from both control and insulin-treated diabetic rats, 1066 +/- 43 mg vs. 904 +/- 16 mg and 959 +/- 36 mg, respectively (P less than 0.01). For comparison, the ODC activity was also investigated in muscle. However, in muscle from diabetic animals the ODC activity declined steadily during the 14 days to 34% of control values (P less than 0.01), and insulin treatment completely normalized the ODC activity in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased ornithine decarboxylase activity in kidneys undergoing hypertrophy in experimental diabetes. 151 80

Renal hypertrophy occurs early in the natural history of human and experimental diabetes and may be a manifestation of the same pathophysiological process which ultimately results in diabetic nephropathy. The precise biological events which stimulate and regulate this growth process remain incompletely understood. We postulated that renal eicosanoids contribute to the development of renal hypertrophy in diabetes. We elected to test the effects of suppression of dienoic eicosanoid metabolism (arachidonic acid metabolism) on renal hypertrophy in diabetic rats by feeding fish oil. Diabetic rats fed fish oil had markedly reduced insulin requirements compared to control rats pair-fed a beef tallow-rich diet. The concentrations of prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 were depressed in the renal cortex of diabetic rats fed fish oil. This alteration in eicosanoid metabolism was associated with a substantial enhancement of diabetic renal hypertrophy. These results indicate that dietary fish oil has profound effects on renal eicosanoid metabolism in experimental diabetes and that these autocoids may participate in the biological events which regulate diabetic renal hypertrophy.
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PMID:Dietary fish oil enhances renal hypertrophy in experimental diabetes. 170 49

We examined the effects of aldose reductase inhibition (ARI) on glomerular filtration rate (GFR), albuminuria, and kidney histology in partially insulin-treated streptozocin-induced diabetic (STZ-D) rats. After 1 mo of diabetes, GFR was elevated over control values in the STZ-D rats but was not affected by treatment with statil (an aldose reductase inhibitor). In another set of rats maintained for 7 mo, albuminuria was significantly increased in the diabetic rats from 2 mo on but was also not affected by statil treatment. Similarly, histological glomerular damage and diabetes-induced kidney hypertrophy were also greater in diabetic animals but were not altered by statil treatment. The frequency of diabetic cataracts was reduced by statil, and erythrocyte and kidney sorbitol levels were normalized, confirming the efficacy of ARI. Thus, inhibition of the aldose reductase pathway with statil does not ameliorate the hemodynamic, proteinuric, histological, or growth abnormalities in this model of diabetic nephropathy.
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PMID:Aldose reductase inhibition and glomerular abnormalities in diabetic rats. 250 60

Renal hypertrophy and elevated glomerular filtration rate (GFR) appeared in early stage of diabetic nephropathy (DN). In order to investigate the effect of Rheum officinale (RO) on the renal hypertrophy, streptozotocin induced diabetic rats with moderate hyperglycemia were divided into two groups, receiving RO (RO-DN) or not (DN), and one group of non-diabetic control (C) was set up. At the 28th day, DN group exhibited heavier kidney weight (+61%), more protein (+133%) and DNA (+94%) contents in the kidney and higher GFR (+94%) than the control. RO-DN rats showed much less above mentioned changes. In addition, lipid abnormalities were ameliorated in RO-DN group. This result suggest that RO is beneficial to the diabetes in terms of renal hypertrophy and GFR changes at early stage and is recommended in the treatment of diabetic nephropathy.
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PMID:[Effects of Rheum on renal hypertrophy and hyperfiltration of experimental diabetes in rat]. 821 81

Renal hypertrophy is a characteristic and early manifestation of diabetes in human and experimental animals. We examined the precise distribution of insulin-like growth factor-I (IGF-I) receptor mRNA in the experimental diabetic rat kidney using a nonradioactive in situ hybridization technique. Expression of IGF-I receptor mRNA was rarely seen in the glomeruli of control rats. IGF-I receptor mRNA was detected after induction of diabetes in glomerular mesangial, visceral epithelial, and parietal epithelial cells. The number of IGF-I receptor mRNA-positive cells in a glomerulus increased significantly at 4 weeks as compared with the control rats. Overexpression of IGF-I receptor in glomerular cells may contribute to the glomerular hypertrophy in diabetic nephropathy.
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PMID:Upregulation of insulin-like growth factor receptor gene in experimental diabetic rat glomeruli. 857 42

Renal hypertrophy is a characteristic and early manifestation of diabetes in humans and experimental animals. We examined the precise distribution of insulin-like growth factor-I (IGF-I) mRNA and IGF-I receptor mRNA in the experimental diabetic rat kidney using a nonradioactive in situ hybridization technique. No significant difference in the distribution of IGF-I mRNA was found between the diabetic and control rats. IGF-I mRNA-positive cells were found in the collecting ducts and in scattered single cells in the distal tubules. The number of IGF-I mRNA-positive cells was very low in the glomeruli. Expression of IGF-I receptor mRNA was rarely seen in the glomeruli of control rats. IGF-I receptor mRNA was detected after induction of diabetes in glomerular mesangial, visceral epithelial, and parietal epithelial cells. The number of IGF-I receptor mRNA-positive cells in a glomerulus increased significantly, peaking at 4 weeks as compared with the control rats. Overexpression of IGF-I receptor in glomerular cells, especially mesangial and visceral epithelial cells, may contribute to glomerular hypertrophy in diabetic nephropathy.
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PMID:Increased gene expression of insulin-like growth factor-i receptor in experimental diabetic rat glomeruli. 873 Apr 36

Cell cycle regulation in diabetic nephropathy. Renal hypertrophy is one of the earliest abnormalities of diabetic nephropathy. Although selected cell populations. such as tubulointerstitial fibroblasts, may undergo sustained proliferation in the diabetic environment, most renal cells such as mesangial cells are arrested in the G1-phase of the cell cycle after actively leaving G0-phase and some self-limited early proliferation. High glucose, transforming growth factor-beta (TGF-beta), angiotensin II, and probably other factors induce inhibitors of cyclin-dependent kinases (CDK) including p21Cip1 and p27KiP1. These CDK-inhibitors bind to and inactivate G1-phase cyclin/CDK complexes. The consequence is a lack in kinase activity, underphosphorylation of the retinoblastoma gene protein, and a failure to initiate the G1-S-phase transit. The half-life of CDK-inhibitors may also be increased by serine phosphorylation mediated through activated MAP kinases. Treatment of diabetic rats with angiotensin-converting enzyme inhibitors attenuates glomerular hypertrophy and abolishes the glomerular expression of the CDK-inhibitors p16INK4 and p27KiP1, thus indicating that the cell cycle arrest can be therapeutically influenced. Cell cycle proteins may also be involved in these molecular events, leading to a limited degree of tubular apoptosis, which is a feature of diabetic nephropathy. Although not definitively proven, accumulating evidence suggests that early hypertrophy of renal cells may act as pacemaker for subsequent irreversible structural changes, such as glomerulosclerosis and tubulointerstitial fibrosis. Therefore, a better understanding of altered processes of cell cycle regulation is necessary to develop novel therapeutic strategies to prevent diabetic nephropathy. The recent observation that glomerular hypertrophy and proteinuria do not develop in diabetic p21CiP1 knockout mice indicates that this approach is feasible.
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PMID:Cell cycle regulation in diabetic nephropathy. 1099 92

In diabetes mellitus (DM), the urine flow rate is increased, and the fluid turnover in the body is accelerated because of the glucose-induced osmotic diuresis. On the other hand, plasma vasopressin (VP) is elevated in both type 1 and type 2 DM. This elevation seems to be due to a resetting of the osmostat. A high VP level is beneficial in the short term because it limits to some extent the amount of water required for the excretion of a markedly enhanced load of osmoles (mainly glucose). However, in the long run, it may have adverse effects by favoring the development of diabetic nephropathy. VP has been shown in normal rats to induce kidney hypertrophy, glomerular hyperfiltration, and an increase in urinary albumin excretion (features also occurring in association in the period preceding diabetic nephropathy). Moreover, VP has been shown to participate in the progression of renal failure in rats with five-sixths reduction in renal mass. In recent studies, we have shown (1) that creatinine clearance, albuminuria and renal mass increased much less during experimental DM in Brattleboro rats unable to secrete VP than in their VP-replete Long-Evans controls, and (2) that albuminuria was prevented during experimental DM in Wistar rats when a VP nonpeptidic, highly selective V2 receptor antagonist was administered chronically for 9 weeks. Taken together, these results strongly suggest that VP plays a crucial role in the onset and aggravation of the renal complications of DM. The mechanisms by which VP exerts these adverse V2-dependent effects are not yet elucidated. They are most likely indirect and may involve several intermediate steps comprising VP-induced changes in the composition of the tubular fluid in the loop of Henle (due to solute recycling in the renal medulla associated with improved concentrating activity of the kidney), inhibition of the tubuloglomerular feedback control of glomerular function, and alterations in glomerular hemodynamics by the intrarenal renin-angiotensin system.
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PMID:Vasopressin and diabetes mellitus. 1117 21

Nitric oxide (NO) is a multifunctional mediator that has been implicated in the short-term hemodynamic alterations that occur in acute streptozocin (STZ)-induced diabetes. We investigated the role of NO produced by inducible nitric oxide synthase (iNOS) in chronic STZ diabetic nephropathy. Diabetes was induced in C57BL/6 and iNOS knockout (KO) mice with two intraperitoneal injections of STZ, 100 mg/kg. Animals were maintained without insulin treatment for 40 weeks. There were no significant differences between the strains in blood urea nitrogen (BUN), serum creatinine or glucose concentration, or urinary protein excretion during the entire observation period. Urinary nitrite + nitrate excretion was significantly lower in iNOS KO mice compared to control animals at all time points; in C57 mice, urinary nitrite declined progressively with more prolonged duration of diabetes. Renal hypertrophy (kidney weight/body weight) was noted in both strains of mice. However, histopathological assessment of renal tissue specimens at 16 and 40 weeks demonstrated increased mesangial hypercellularity and expansion as well as more prominent tubulointerstitial fibrosis in iNOS KO versus C57 mice. These changes were accompanied by increased interstitial deposition of type I collagen at 16 and 40 weeks in iNOS KO mice. Glomerular basement membrane staining for type IV collagen was also increased at 40 weeks in diabetic iNOS KO mice. While iNOS protein was undetectable in any of the kidney specimens obtained from either strain, eNOS was present throughout the course of chronic STZ diabetes. Moreover, eNOS expression was significantly increased by approximately 40% at 16 and 40 weeks of observation in iNOS KO versus C57 mice. There was no difference in renal cortical malondialdehyde content between the strains early or late in the disease course. In time control animals, there was no evidence of renal histopathological damage in iNOS KO or C57 mice after 40 weeks. We conclude that iNOS-derived NO modulates glomerulosclerosis and tubulointerstitial fibrosis in chronic STZ nephropathy. This action is probably a result of the direct actions of NO on the synthesis and degradation of extracellular matrix proteins.
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PMID:Chronic diabetic nephropathy: role of inducible nitric oxide synthase. 1179 30

It was previously reported that transgenic (mRen-2)27 rats with streptozotocin-induced diabetes mellitus progressively develop advanced nephropathy in 12 wk. These lesions are largely prevented when the angiotensin-converting enzyme inhibitor perindopril is administered from the time of induction of diabetes mellitus. This study aimed to determine the lowest dose of early perindopril treatment required for substantial improvement of renal function and structure and to investigate whether late intervention prevents or reverses the progression of established renal lesions. At 6 wk of age, female heterozygous Ren-2 rats were randomized to receive either streptozotocin (diabetic) or citrate buffer (control). Rats were gavaged, beginning early after the induction of diabetes mellitus or the administration of control vehicle, with 0, 0.02, 0.2, or 2 mg/kg per d perindopril for 12 wk. A separate group of diabetic Ren-2 rats received late treatment with 2 mg/kg per d perindopril throughout week 8 to week 12, when rats were hypertensive and albuminuric and exhibited increased kidney weight and glomerulosclerotic index (GSI). Among diabetic rats, early 0.02 mg/kg per d perindopril treatment reduced systolic BP, GSI, and renal collagen staining but had no effect on albuminuria or kidney hypertrophy. Early 0.2 or 2 mg/kg per d perindopril treatment further reduced systolic BP, GSI, and renal collagen staining and decreased albuminuria and kidney hypertrophy. Late intervention was as antihypertensive and antialbuminuric as early 0.2 or 2 mg/kg per d perindopril treatment but did not prevent a moderate increase in GSI. In conclusion, early treatment with 0.2 mg/kg per d perindopril was the lowest dosage to largely prevent severe diabetic nephropathy in transgenic Ren-2 rats. Late-onset perindopril treatment of diabetic rats with established nephropathy was as efficacious as early treatment with respect to various renal parameters, such as albuminuria, but was associated with moderate progression of glomerulosclerosis.
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PMID:Effects of low-dose and early versus late perindopril treatment on the progression of severe diabetic nephropathy in (mREN-2)27 rats. 1185 72


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