Sodium-Hydrogen Antiport, Cell Function and Susceptibility to Diabetic Nephropathy

1996 ◽  
pp. 215-222
Author(s):  
Roberto Trevisan ◽  
GianCarlo Viberti
Keyword(s):  
Diabetic Nephropathy ◽  
Cell Function ◽  
Sodium Hydrogen

scholarly journals Alteration of urinary sorbitol excretion in WBN-kob diabetic rats - treatment with an aldose reductase inhibitor

2004 ◽  
Vol 181 (3) ◽  
pp. 429-435 ◽  
Author(s):  
T Tsugawa ◽  
R Shinohara ◽  
A Nagasaka ◽  
I Nakano ◽  
F Takeda ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Aldose Reductase ◽  
Whole Blood ◽  
Reductase Inhibitor ◽  
Cell Function ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Aldose Reductase Inhibitor ◽  
Tubular Damage ◽  
Renal Tubules

An accelerated polyol pathway in diabetes contributes to the development of diabetic complications. To elucidate diabetic nephropathy involving also renal tubular damage, we measured urinary sorbitol concentration concomitantly with urinary N-acetyl-D-glucosaminidase (NAG) excretion in WBN-kob diabetic rats.Twenty-four-hour urinary sorbitol concentrations increased in the diabetic rats in parallel with whole blood sorbitol concentrations. An increase in 24-h urinary NAG excretion coincided with the elevated urinary sorbitol levels in the diabetic rats. The administration of epalrestat, an aldose reductase inhibitor, reduced the increased whole blood and urinary sorbitol concentrations and urinary NAG excretion concomitantly with renal aldose reductase inhibition in the diabetic rats.These results indicate that diabetic nephropathy involves distorted cell function of renal tubules, and that treatment with epalrestat may prevent at least the progress of the nephropathy.

scholarly journals Increased DAAM2, a new podocyte-associated protein, in diabetic nephropathy

2021 ◽  
Author(s):  
Chenyang Qi ◽  
Faten Al Somali ◽  
Jinyong Zhong ◽  
Raymond C Harris ◽  
Valentina Kon ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Cell Function ◽  
Enzyme Inhibitor ◽  
Normal Donor ◽  
Rna Seq ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Glomerular Size ◽  
Normal Human ◽  
Human And Mouse

Abstract Background Previously, by using proteomic analysis and RNA-seq in isolated glomeruli, we identified several novel differentially expressed proteins in human and mouse diabetic nephropathy (DN) vs control, including DAAM2. DAAM2, the disheveled associated activator of morphogenesis 2 protein, binds the Wnt effector Disheveled. We now aimed to study possible contributions of DAAM2 to DN. Methods We assessed DAAM2 by immunostaining in non-cancer regions of human nephrectomy (Nx), DN and normal donor kidney tissues. We also examined DAAM2 in DN mice (db/db/eNOS-/-) and Nx mice. DN mice treated with angiotensin converting enzyme inhibitor (ACEI) or dipeptidyl peptidase 4 inhibitor (DPP4I) or vehicle were compared. DAAM2 was knocked down in primary cultured podocytes by siRNA to study its effects on cell function. Results In normal human glomeruli, DAAM2 was expressed only on podocytes. DAAM2 expression was increased in both Nx and DN vs normal donors. Podocyte DAAM2 expression was increased in DN and Nx mouse models. Glomerular DAAM2 expression correlated with glomerular size and was decreased significantly by ACEI, while DPP4I only numerically reduced DAAM2. In primary cultured podocytes, knock down of DAAM2 enhanced adhesion, slowed migration, activated Wnt/β-catenin signaling and downregulated mTORC1 and Rho activity. Conclusions Podocyte DAAM2 is upregulated in both nephrectomy and DN, which could be contributed to by glomerular hypertrophy. We hypothesize that DAAM2 regulates podocyte function through the mTORC1, Wnt/β-catenin and Rho signaling pathways.

scholarly journals Aberrant production of extracellular matrix proteins and dysfunction in kidney endothelial cells with a short duration of diabetes

2013 ◽  
Vol 304 (1) ◽  
pp. F19-F30 ◽  
Author(s):  
Cathy Grutzmacher ◽  
SunYoung Park ◽  
Yun Zhao ◽  
Margaret E. Morrison ◽  
Nader Sheibani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Diabetic Nephropathy ◽  
Endothelial Cell ◽  
Short Duration ◽  
Cell Function ◽  
Matrix Proteins ◽  
Endothelial Cell Function ◽  
Duration Of Diabetes ◽  
Akita Mice

Diabetic nephropathy is the most common cause of end-stage renal disease and is a major risk factor for cardiovascular disease. In the United States, microvascular complications during diabetic nephropathy contribute to high morbidity and mortality rates. However, the cell-autonomous impact of diabetes on kidney endothelial cell function requires further investigation. Male Akita/+ [autosomal dominant mutation in the insulin II gene (Ins2)] mice reproducibly develop diabetes by 4 wk of age. Here, we examined the impact a short duration of diabetes had on kidney endothelial cell function. Kidney endothelial cells were prepared from nondiabetic and diabetic mice (4 wk of diabetes) to delineate the early changes in endothelial cell function. Kidney endothelial cells from Akita/+ mice following 4 wk of diabetes demonstrated aberrant expression of extracellular matrix proteins including decreased osteopontin and increased fibronectin expression which correlated with increased α5-integrin expression. These changes were associated with the attenuation of migration and capillary morphogenesis. Kidney endothelial cells from Akita/+ mice had decreased VEGF levels but increased levels of endothelial nitric oxide synthase(eNOS) and NO, suggesting uncoupling of VEGF-mediated NO production. Knocking down eNOS expression in Akita/+ kidney endothelial cells increased VEGF expression, endothelial cell migration, and capillary morphogenesis. Furthermore, attenuation of sprouting angiogenesis of aortas from Akita/+ mice with 8 wk of diabetes was restored in the presence of the antioxidant N-acetylcysteine. These studies demonstrate that aberrant endothelial cell function with a short duration of diabetes may set the stage for vascular dysfunction and rarefaction at later stages of diabetes.

scholarly journals Endoglin Promotes Myofibroblast Differentiation and Extracellular Matrix Production in Diabetic Nephropathy

2020 ◽  
Vol 21 (20) ◽  
pp. 7713
Author(s):  
Tessa Gerrits ◽  
Malu Zandbergen ◽  
Ron Wolterbeek ◽  
Jan A. Bruijn ◽  
Hans J. Baelde ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Cell Function ◽  
Interstitial Fibrosis ◽  
Human Kidney ◽  
Fibroblast Cell ◽  
Diabetic Patients ◽  
Endothelial Cell Function ◽  
Intestinal Fibrosis ◽  
Kidney Fibroblast ◽  
Sirius Red

Diabetic nephropathy (DN) is a complication of diabetes mellitus that can lead to proteinuria and a progressive decline in renal function. Endoglin, a co-receptor of TGF-β, is known primarily for regulating endothelial cell function; however, endoglin is also associated with hepatic, cardiac, and intestinal fibrosis. This study investigates whether endoglin contributes to the development of interstitial fibrosis in DN. Kidney autopsy material from 80 diabetic patients was stained for endoglin and Sirius Red and scored semi-quantitatively. Interstitial endoglin expression was increased in samples with DN and was correlated with Sirius Red staining (p < 0.001). Endoglin expression was also correlated with reduced eGFR (p = 0.001), increased creatinine (p < 0.01), increased systolic blood pressure (p < 0.05), hypertension (p < 0.05), and higher IFTA scores (p < 0.001). Biopsy samples from DN patients were also co-immunostained for endoglin together with CD31, CD68, vimentin, or α-SMA Endoglin co-localized with both the endothelial marker CD31 and the myofibroblast marker α-SMA. Finally, we used shRNA to knockdown endoglin expression in a human kidney fibroblast cell line. We found that TGF-β1 stimulation upregulated SERPINE1, CTGF, and ACTA2 mRNA and α-SMA protein, and that these effects were significantly reduced in fibroblasts after endoglin knockdown. Taken together, these data suggest that endoglin plays a role in the pathogenesis of interstitial fibrosis in DN.

scholarly journals Clinical Characteristics, Residual Beta-Cell Function and Pancreatic Auto-Antibodies in Thai people with Long-Standing Type 1 Diabetes Mellitus

2020 ◽  
Vol 35 (2) ◽  
pp. 158-162
Author(s):  
Yotsapon Thewjitcharoen ◽  
◽  
Sirinate Krittiyawong ◽  
Somboon Vongterapak ◽  
Soontaree Nakasatien ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Beta Cell ◽  
Diabetic Complications ◽  
Beta Cell Function ◽  
Cell Function ◽  
Hdl Cholesterol ◽  
Protective Effects ◽  
Cross Sectional ◽  
C Peptide ◽  
Triglyceride Concentration

Objectives. To describe the characteristics of long-standing T1DM in Thai patients and assess residual beta-cell function with status of pancreatic autoantibodies. Methodology. This is a cross-sectional study of Thai subjects with T1DM and disease duration ≥25 years seen at the Theptarin Hospital. Random plasma C-peptide and pancreatic auto-antibodies (Anti-GAD, Anti-IA2, and Anti-ZnT8) were measured. Patients who developed complications were compared with those who remained free of complications. Results. A total of 20 patients (males 65%, mean age 49.4±12.0 years, BMI 22.5±3.1 kg/m2, A1C 7.9±1.6%) with diabetes duration of 31.9±5.1 years were studied. Half of the participants remained free from any diabetic complications while the proportions reporting retinopathy, nephropathy, and neuropathy were 40%, 30%, and 15%, respectively. HDL cholesterol was significantly higher and triglyceride concentration significantly lower in patients who were free from diabetic nephropathy but not in those who were free from other complications. The prevalence rates of anti-GAD, anti-IA2, and anti-ZnT8 were 65%, 20%, and 10%, respectively. None of the patients who tested negative for both anti-GAD and anti-IA2 was positive for anti-ZnT8. Residual beta-cell function based on detectable random plasma C-peptide (≥0.1 ng/mL) and MMTT was found in only 3 patients (15%). There was no relationship between residual beta-cell function and protective effects of diabetic complications. Conclusion. Endogenous insulin secretion persists in some patients with long-standing T1DM and half of longstanding T1DM in Thai patients showed no diabetic complications. HDL cholesterol was significantly higher and triglyceride concentration significantly lower in patients who were free from diabetic nephropathy.

Freeze-substitution of rye grass and ragweed pollen grains

1990 ◽  
Vol 48 (3) ◽  
pp. 686-687
Author(s):  
Liza B. Martinez ◽  
Susan M. Wick
Keyword(s):  
Cell Function ◽  
Pollen Grains ◽  
Freeze Substitution ◽  
Cell Types ◽  
Rapid Freezing ◽  
Rye Grass ◽  
Acrylic Resins ◽  
Allergenic Proteins ◽  
Cold Embedding ◽  
Structural Preservation

Rapid freezing and freeze-substitution have been employed as alternatives to chemical fixation because of the improved structural preservation obtained in various cell types. This has been attributed to biomolecular immobilization derived from the extremely rapid arrest of cell function. These methods allow the elimination of conventionally used fixatives, which may have denaturing or “masking” effects on proteins. Thus, this makes them ideal techniques for immunocytochemistry, in which preservation of both ultrastructure and antigenicity are important. These procedures are also compatible with cold embedding acrylic resins which are known to increase sensitivity in immunolabelling.This study reveals how rapid freezing and freeze-substitution may prove to be useful in the study of the mobile allergenic proteins of rye grass and ragweed. Most studies have relied on the use of osmium tetroxide to achieve the necessary ultrastructural detail in pollen whereas those that omitted it have had to contend with poor overall preservation.

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