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7 záznamů v Medvik Filtry

Článek

NOS3 894G>T polymorphism is associated with progression of kidney disease and cardiovascular morbidity in type 2 diabetic patients: NOS3 as a modifier gene for diabetic nephropathy

Kidney & blood pressure research. 2013 ; 38 (1) : 92-98.

Kidney Blood Press Res
ISSN 1423-0143
Medvik
Zdroj

BACKGROUND/AIMS: We have previously associated SNP 894G>T in the NOS3 gene with diabetic nephropathy (DN) using multi-locus analysis. Variant 894G>T has been widely studied as a DN susceptibility factor with contradictory results. In the present study we genotyped 894G>T in the cohort of prospectively followed type 2 diabetics with the aim to investigate its possible role in the progression of DN and development of morbidity and mortality associated with diabetes. METHODS: 311 subjects with defined stage of DN were enrolled in the study and followed up for a median of 38 months. We considered three end-points: progression of DN, major cardiovascular event and all-cause mortality. RESULTS: Considering baseline GFR, age at enrolment and diabetes duration as confounders, Cox regression analysis identified 894GT genotype as a risk factor for DN progression (HR = 1.843 [95% CI 1.088 - 3.119], P = 0.023) and 894TT genotype as a risk factor for major cardiovascular event (HR = 2.515 [95% CI 1.060 - 5.965], P = 0.036). CONCLUSION: We ascertained the significant effect of the NOS3 894G>T variant on DN progression and occurrence of major cardiovascular event in T2DM subjects. Based on these results NOS3 can be considered a modifier gene for DN.

MeSH
diabetes mellitus 2. typu enzymologie genetika MeSH
diabetická kardiomyopatie enzymologie epidemiologie genetika MeSH
diabetické nefropatie enzymologie epidemiologie genetika MeSH
hodnoty glomerulární filtrace MeSH
kohortové studie MeSH
lidé středního věku MeSH
lidé MeSH
následné studie MeSH
polymorfismus genetický genetika MeSH
progrese nemoci MeSH
prospektivní studie MeSH
senioři MeSH
synthasa oxidu dusnatého, typ III genetika MeSH
Check Tag
lidé středního věku MeSH
lidé MeSH
mužské pohlaví MeSH
senioři MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Článek

Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy

Nephrology, dialysis, transplantation. 2011 ; 26 (4) : 1229-36.

Nephrol Dial Transplant
ISSN 1460-2385
Medvik
Zdroj

BACKGROUND: Pentose phosphate pathway (PPP) represents a potentially 'protective' mechanism in hyperglycaemia due to shunting of glycolytic intermediates into PPP reactions. We hypothesized that thiamine status (plasma and erythrocyte levels of thiamine and its esters) together with genetic variability in key PPP enzymes-transketolase (TKT), transaldolase and TKT-like-might contribute to the progression of diabetic nephropathy (DN) and mortality of diabetics. METHODS: A total of 240 diabetic subjects with variable degree of kidney disease were included at baseline and were followed up for a median of 26 (IQR 21-50) months. Concentrations of thiamine in plasma and whole blood and TKT-catalysed reaction were determined by HPLC. Single-nucleotide polymorphisms (SNPs) (n = 14) were genotyped by means of PCR using TaqMan chemistry (Applied Biosystems, Foster City, CA, USA). RESULTS: Significant differences in pTh, pThDP, eryThDP and eryTKT between DN-stage groups were ascertained (P < 0.05) with advancing stage of DN being accompanied with increasing values of pTh, pThDP and eryTKT but not eryThDP. A highly significant negative correlation (r = - 0.41, P < 0.001) was found between pThDP and eryThDP, and the tertiles of the ratio of eryThDP/pThDP were significantly associated with all-cause mortality rates (P = 0.0072). We also identified significant differences in the rate of DN progression between different pTDP tertile groups (P = 0.0017). No significant genetic effects were found. CONCLUSIONS: The results support the role of 'functional' thiamine deficiency in the development of hyperglycaemia-related pathology. Limited intracellular availability of active TKT co-factor seems to be a dominant abnormality.

MeSH
diabetické nefropatie enzymologie genetika mortalita MeSH
dospělí MeSH
erytrocyty enzymologie MeSH
genotyp MeSH
glukosa metabolismus MeSH
jednonukleotidový polymorfismus genetika MeSH
lidé středního věku MeSH
lidé MeSH
míra přežití MeSH
následné studie MeSH
pentosafosfáty metabolismus MeSH
pentózofosfátový cyklus MeSH
průřezové studie MeSH
senioři MeSH
thiamin metabolismus MeSH
transaldolasa genetika MeSH
transketolasa genetika MeSH
Check Tag
dospělí MeSH
lidé středního věku MeSH
lidé MeSH
mužské pohlaví MeSH
senioři MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Článek

Nové aspekty systému renin-angiotensin: angiotensin-konvertující enzym 2 jako potenciální cíl léčby hypertenze a diabetické nefropatie
[New aspects of the renin-angiotensin system: angiotensin-converting enzyme 2 - a potential target for treatment of hypertension and diabetic nephropathy]

Current Opinion in Nephrology and Hypertension (České vyd.). 2008 ; 2 (3) : 61-67.

ISSN 1802-3827
Medvik
Zdroj

Whereas angiotensin-converting enzyme promotes the formation of angiotensin II, angiotensin-converting enzyme 2 promotes the degradation of angiotensin II to angiotensin-(1-7). We review recent studies dealing with angiotensin-converting enzyme 2 in kidney disease and hypertension, and discuss the potential therapeutic benefit of increasing angiotensin-converting enzyme 2 activity in the treatment of these diseases. RECENT FINDINGS: In glomeruli from diabetic mice, angiotensin-converting enzyme 2 expression is downregulated, and pharmacological inhibition of angiotensin-converting enzyme 2 leads to worsening of albuminuria, increased mesangial matrix deposition and fibronectin expression. The deletion of the angiotensin-converting enzyme 2 gene in mice leads to worsening of angiotensin II-induced hypertension and has also been shown to cause glomerulosclerosis in aging male mice. SUMMARY: Angiotensin-converting enzyme 2 is a key enzyme in the renin-angiotensin system that favors the degradation of angiotensin I and angiotensin II. Angiotensin-converting enzyme 2 inhibition by pharmacological means and by genetic deletion worsens kidney disease in diabetic mice. Strategies geared to increasing angiotensin-converting enzyme 2 activity may provide a novel therapeutic target within the renin-angiotensin system by enhancing angiotensin II degradation that may complement the current approach of inhibiting angiotensin II formation and action. Amplifying angiotensin-converting enzyme 2 activity may have a potential therapeutic role for kidney disease and hypertension.

Článek

Renal activity of Akt kinase in experimental Type 1 diabetes

Physiological research. 2008 ; 57 (5) : 709-715.

Medvik
Zdroj

Akt kinase regulates numerous cell functions including glucose metabolism, cell growth, survival, protein synthesis, and control of local hemodynamics. mTOR is one of down-stream effectors of Akt involved in the initiation of protein translation. However, renal Akt signaling in Type 1 diabetes (DM) in vivo, in particular under the conditions reflecting differences in metabolic control, has received less attention. Renal cortical activity and expression of Akt and mTOR (kinase assay, western blotting) were determined in streptozotocin-diabetic rats (D) with different levels of glycemic control (blood glucose 22.0±1.0, 13.4±1.5, 8.1±0.4 mmol/l, p<0.05 between the groups), achieved by varying insulin treatment (0, 4 and 12 IU/day), and in control rats with (C4) or without (C) chronic insulin administration. Renal Akt activity was reduced in D rats without insulin treatment and severe hyperglycemia (D-0, -62 %, p<0.01 vs. C), partially restored in moderately hyperglycemic rats (D-4, -30 %, p<0.05 vs. C), and normalized in D rats with intensive insulin and tight metabolic control (D-12). Expression of active mTOR paralleled Akt activity in D-0 (-51 %, p<0.01 vs. C), but not in D-4 and D- 12 that demonstrated increases in active mTOR (+55 %, +80 % resp., p<0.05) as compared to C. Moreover, insulin activated renal Akt (+82 %, p<0.01), but not mTOR in C4. In conclusion, glycemic control and intensity of insulin treatment are important modulators of renal Akt and mTOR activity in diabetes. While Akt activity is reversible by tight metabolic control, combination of hyperglycemia and insulin treatment resulted in enhancement of mTOR activity. In addition to Akt, other signaling pathways likely contribute to regulation of renal mTOR activity in diabetes.