Disease relevance of Diabetic Nephropathies

• Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy [1].
• To evaluate the role of hyperglycemia in the pathogenesis of diabetic nephropathy, the kidneys from dogs experimentally galactosemic for 5 yr have been compared with the kidneys from age-matched normal dogs and dogs with alloxan-induced diabetes for 5 yr [2].
• While both drugs are known for their different mechanisms of action, the fact that both prevent diabetes-related increases in glomerular PKC activity and albuminuria supports the hypothesis that PKC plays a central role in the development of diabetic nephropathy [3].
• Despite the potentially protective effects of estrogen on bone and cardiovascular tissue as well as against kidney diseases, its effects on diabetic nephropathy are unknown [4].
• In view of the major alterations which take place at the level of the extracellular matrix of the glomerular wall in diabetes mellitus and the key roles played by beta 1 integrins in cell-to-matrix interactions, it is imperative to understand the role played by integrins in the development of diabetic glomerulosclerosis [5].

Psychiatry related information on Diabetic Nephropathies

• In the Irbesartan Diabetic Nephropathy Trial (IDNT), the beneficial effect of irbesartan was mainly against the doubling of the baseline creatinine concentration (37% risk reduction) but there was also a 20% reduction in the onset of ESRD [6].

High impact information on Diabetic Nephropathies

• Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy [7].
• This review focuses on the metabolic factors beyond blood glucose that are involved in the pathogenesis of diabetic kidney disease, i.e., advanced glycation end-products and the aldose reductase system [8].
• Prevention of diabetic nephropathy in db/db mice with glycated albumin antagonists. A novel treatment strategy [9].
• We postulate that the interception of the glomerular activity of TGF-beta may be an effective intervention in the management of diabetic nephropathy [10].
• 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors prevent high glucose-induced proliferation of mesangial cells via modulation of Rho GTPase/ p21 signaling pathway: Implications for diabetic nephropathy [11].

Chemical compound and disease context of Diabetic Nephropathies

• The experimental model of streptozotocin-induced diabetes in rats was utilized to determine the biosynthetic and biochemical alterations in the proteoglycans of the glomerular extracellular matrices (glomerular basement membrane and mesangial matrix) in diabetic nephropathy [12].
• Thus, this study provides a molecular basis for the use of statins, independently of their cholesterol-lowering effect, in early stages of diabetic nephropathy [11].
• ACE inhibitors and angiotensin II-AT1 receptor blockers appear to confer similar benefits in experimental diabetic nephropathy, and bradykinin-B2 receptor blockers do not influence this effect [13].
• The effects of perindopril and triple therapy in a normotensive model of diabetic nephropathy [14].
• The concurrent changes in plasma levels of three IgA-containing species in the untreated STZ-induced diabetic rat and the demonstration of abnormal immunoreactive IgA-containing renal glomerular deposits make this experiment an attractive model for studying the possible role of disturbed IgA metabolism in the pathogenesis of diabetic nephropathy [15].
• Both perindopril and aliskiren reduced blood pressure, albuminuria and structural injury in experimental diabetic nephropathy, although not to the same extent [16].

Biological context of Diabetic Nephropathies

• Finally, screening for diabetic kidney disease among IDDM patients should include determination of glomerular filtration rate and measurement of UAE and blood pressure, especially among women [17].
• We conclude that L-PGDS plays an important role regulating insulin sensitivity and atherosclerosis in type 2 diabetes and may represent a novel model of insulin resistance, atherosclerosis, and diabetic nephropathy [18].
• Thus, similar to human diabetic nephropathy, ICER Igamma transgenic mice exhibit a stable and progressive phenotype of diabetic kidney disease due solely to chronic hyperglycemia without other modulating factors [19].
• Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial [20].
• To clarify the mechanism of early diabetic nephropathy, we measured [3H]-thymidine incorporation and cell numbers to show the influence of a high ambient glucose concentration and the osmotic effect on rat mesangial cell proliferation [21].

Anatomical context of Diabetic Nephropathies

• Diabetic nephropathy ensues from events involving earliest changes in the glomeruli and podocytes, followed by accumulation of extracellular matrix in the mesangium [22].
• Studies of human diabetic glomerulosclerosis with a newly devleoped guanidine method have revealed that, like renal tubules, thickening of the glomerular capillary basal lamina is due exclusively to inordinate accumulation of the epithelial basal lamina [23].
• Of special interest is the induction of large amounts of AR in rat kidney cortex mesangial cells, a target tissue of diabetes and a site where excessive accumulation of sorbitol is suspected to be a critical factor in diabetic nephropathy [24].
• The manner in which nephrons degenerate in diabetic nephropathy and whether the injury could be transferred from nephron to nephron are insufficiently understood [25].
• To elucidate the role of macrophages in diabetic glomerulosclerosis (DGS), an immunohistologic study was performed using monoclonal antibodies to common leukocyte antigen (DAKO-LC), T cells (T3), B cells (CD22), and macrophages (MAC 387, Leu-M5, and EBM-11) [26].

Gene context of Diabetic Nephropathies

• Activated MAPK, in turn, may induce various functional changes of mesangial cells at least through the activation of cPLA2 and contribute to the development of diabetic nephropathy [27].
• Recently, we showed that the overexpression of type IV collagen (Col IV), a major component of mesangial extracellular matrix, is transcriptionally regulated by Smad1 in diabetic glomerulosclerosis [28].
• However, the phenotypic change in D-NOD cells is associated with constitutive activation of the IGF-I signaling pathways, which may participate in the development and progression of diabetic glomerulosclerosis [29].
• The present study suggests that specific GHR blockade may present a new concept in the treatment of diabetic kidney disease [30].
• Exposure of MC to TGF-beta, increased glucose concentrations, or cyclic mechanical strain, all causal factors in diabetic glomerulosclerosis, markedly induced the expression of CTGF transcripts, while recombinant human CTGF was able to autoinduce its own expression [31].
• In a sex-specific sub-analysis, the variants rs979972 and rs749701 in the first intron of ACTN4 were nominally associated with diabetic nephropathy in females, with odds ratios of 1.81 (95% CI 1.18-2.79, p = 0.007) and 1.93 (95% CI 1.26-2.96, p = 0.003) respectively [32].

Analytical, diagnostic and therapeutic context of Diabetic Nephropathies

• Inhibition of long chain fat oxidation in the db/db mouse results in significant lowering of blood glucose, and decreased the renal immunopathologic features of diabetic nephropathy in this animal model [33].
• Cell culture in high ambient glucose has been used as a model in elucidating cellular mechanisms underlying diabetic nephropathy [34].
• We conclude that nephrin is connected to the early changes of diabetic nephropathy and thus may contribute to the loss of glomerular filtration function [35].
• 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 [36].
• In this study we examined the effect of green tea polyphenols (GTP) and partially hydrolysed guar gum (PHGG) as dietary fibre on diabetic nephropathy, using rats that had been subjected to subtotal nephrectomy and injection of streptozotocin [37].

References