Kidney involvement in a nongenetic rat model of type 2 diabetes

Danda, R S; Habiba, Nusrath; Rincon-Choles, Hernan; Bhandari, Basant; Barnes, Jeffrey L.; Abboud, Hanna E.; Pèrgola, Pablo E.

doi:10.1111/j.1523-1755.2005.00727.x

Cited by 118 publications

(95 citation statements)

References 31 publications

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“…We have shown that rats with dyslipidemia develop glomerular dysfunction, proteinuria and structural changes in kidney. In agreement with our findings, Danda et al 23 reported that high fat diet alone causes significant kidney damage in rats. Our findings suggest that the degree of proteinuria, elevated level of serum creatinine and decrease in the creatinine clearance, which is an ultimate indicator of the GFR, may be adequate markers of renal insufficiency induced by dyslipidemia and atherogenic factors.…”

Section: Discussionsupporting

confidence: 83%

Tocotrienols have a nephroprotective action against lipid-induced chronic renal dysfunction in rats

et al. 2014

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Vitamin E is the generic term for a group of tocopherols and tocotrienols (T3). Hyperlipidemia has been known to cause progressive chronic renal dysfunction (CRD). Several investigators have reported that T3 have hypolipidemic and nephroprotective activity against free radicalrelated diseases. This study was conducted to determine if T3 as tocotrienol-rich fraction (TRF) from palm oil would protect against lipid-induced CRD in rats. For the induction of atherosclerosis and hyperlipidemia, Wistar male rats were fed an atherogenic diet containing 1.25% cholesterol, 0.5% cholic acid and 21% beef tallow (42.6% calories from fat). The atherogenic diet was given for 14 weeks to induce atherosclerosis. The control rats were given normal rat chow and drug control animals treated with TRF (100 mg/kg bw; orally). The first group was taken as disease control in which the animals were left untreated and given normal rat chow for six weeks, while the second group was treated with 100 mg TRF/kg bw. Atherosclerosis and renal functions were evaluated after six weeks of TRF treatment. Feeding an atherogenic diet to rats for 14 weeks resulted in dyslipidemia and impaired renal functions with decreased glomerular filtration rate. The treatment with TRF significantly reduced dyslipidemia and inhibited the development of CRD caused by atherogenic factors. These findings show that low-dose treatment of TRF may provide significant health benefits in the prevention of lipidinduced CRD. The study suggests that TRF is effective in preventing lipid-induced CRD.

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Section: Discussionsupporting

confidence: 83%

Tocotrienols have a nephroprotective action against lipid-induced chronic renal dysfunction in rats

et al. 2014

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“…Much evidence has accumulated to confirm that high glucose induces TGF-␤1 in kidney tubule cells. 4,21,22 Although high glucose significantly upregulates Txnip, unexpectedly, our data demonstrate that TGF-␤1 decreases Txnip expression in HK-2 cells. Consistent with this observation, effective silencing of TGF-␤1 in proximal tubular cells leads to an enhancement of Txnip expression.…”

Section: Discussionmentioning

confidence: 77%

High Glucose-Induced Thioredoxin-Interacting Protein in Renal Proximal Tubule Cells Is Independent of Transforming Growth Factor-β1

Chen

Gilbert

et al. 2007

The American Journal of Pathology

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“…To investigate the effect of diabetes on tuberin function and expression of fibronectin in vitro, PPTECs isolated from the kidney cortex of wild-type and TSC2 +/2 rats were exposed to HG (25 and wild-type diabetic animals compared with control rats. **P,0.01, significant difference from control animals to diabetic animals; *P,0.05, difference between TSC2 +/2 rats to wild-type rats; # P,0.05, differences between diabetic insulin-treated diabetic rats.…”

Section: Hg Enhances Akt and Tuberin Phosphorylation And Results In Fmentioning

confidence: 99%

“…§ P,0.01, significant differences between NG and HG; ¶ P,0.01, differences in rapamycin-treated cells and nontreated cells; an Olympus auto analyzer (AU640; Olympus Corp, Melville, NY) as previously described. 25 Creatinine clearance was calculated according to standard formulas. Albumin was measured in the 24-hour urine collection of each animal by an ELISA ALPCO kit (Salem, NH).…”

Section: Animalsmentioning

confidence: 99%

Tuberin Inhibits Production of the Matrix Protein Fibronectin in Diabetes

Habib

Yadav²,

Tizani³

et al. 2012

Journal of the American Society of Nephrology

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Exposure of proximal tubular epithelial cells to high glucose contributes to the accumulation of tubulointerstitial and matrix proteins in diabetic nephropathy, but how this occurs is not well understood. We investigated the effect of the signaling molecule tuberin, which modulates the mammalian target of rapamycin pathway, on renal hypertrophy and fibronectin expression. We found that the kidney mass was significantly greater in partially tuberin-deficient (TSC2 +/2 ) diabetic rats than wild-type diabetic rats. Furthermore, TSC2 +/2 rats exhibited significant increases in the basal levels of phospho-tuberin and fibronectin expression in the kidney cortex. Increased levels of phosphorylated tuberin associated with an increase in fibronectin expression in both wild-type and TSC2 +/2 diabetic rats. Treatment with insulin abrogated the diabetes-induced increase in fibronectin expression. In vitro, high glucose enhanced fibronectin expression in TSC2 +/2 primary proximal tubular epithelial cells; both inhibition of Akt and inhibition of the mammalian target of rapamycin could prevent this effect of glucose. In addition, forced expression of tuberin in tuberin-null cells abolished the expression of fibronectin protein. Taken together, these data suggest that tuberin plays a central role in the development of renal hypertrophy and in modulating the production of the matrix protein fibronectin in diabetes.

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Kidney involvement in a nongenetic rat model of type 2 diabetes

Cited by 118 publications

References 31 publications

Tocotrienols have a nephroprotective action against lipid-induced chronic renal dysfunction in rats

Tocotrienols have a nephroprotective action against lipid-induced chronic renal dysfunction in rats

High Glucose-Induced Thioredoxin-Interacting Protein in Renal Proximal Tubule Cells Is Independent of Transforming Growth Factor-β1

Tuberin Inhibits Production of the Matrix Protein Fibronectin in Diabetes

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