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Peroksizom Proliferatör ile Etkinleştirilen Reseptörlerin İnsülin Direnci ve Septik Şok Patojenezindeki Rolü

Year 2015, Volume: 5 Issue: 4, 247 - 258, 29.12.2015
https://doi.org/10.5455/musbed.20150715121617

Abstract

Peroksizom proliferatör ile etkinleştirilen reseptörler ligant ile etkin¬leştirilen transkripsiyon faktörleridir ve sınıf II nükleer reseptör ailesine aittirler. Günümüze dek peroksizom proliferatör ile etkinleştirilen resep¬tör (peroxisome proliferator-activated receptor; PPAR) α, PPARβ ve PPARγ olmak üzere 3 alt tür tanımlanmıştır. PPARα başlıca lipit metabolizması ve enflamatuvar sürecin düzenlenmesinde rol oynamaktadır. PPARα ve PPARγ üzerine yapılan çok sayıdaki çalışmaya karşın, PPARβ’nın işlevsel kimliği henüz netlik kazanmamıştır; çünkü neredeyse tüm dokularda eksprese edilmektedir. PPARγ ise glukoz homeostazı ve adipojenezin düzenlenmesinde anahtar rol oynar. İnsülin direnci kandaki normal ya da yüksek insülin düzeyine rağmen, zayıf biyolojik yanıt oluşmasıdır. İnsülin direncinde başta kas, yağ ve karaciğer olmak üzere tüm dokularda insü¬line gerekli ve yeterli yanıt oluşmamaktadır. PPARα lipit metabolizması üzerine etkili genleri düzenleyerek, PPARγ ise çeşitli mekanizmalar ile glukoz homeostazını sağlayarak insülin direnci ortaya çıkmasını engeller. Sepsis, bilinen veya olası bir enfeksiyona karşı verilen sistemik enflama-tuvar yanıt durumu, septik şok ise intravenöz sıvı uygulamasına yanıtsız hipotansiyonun eşlik ettiği şiddetli sepsistir. PPAR agonistleri ile yapılan klinik öncesi çalışmalarda sepsis ve septik şok patojenezinde rol oynayan nükleer faktör κB ve etkinleştirici protein-1 gibi transkripsiyon faktörle-rinin etkinleşmesi inhibe edilerek proenflamatuvar gen ekspresyonunun engellendiği görülmüştür. Bu derlemede, insülin direnci ve septik şok patojenezinde PPAR’ların rolüne değinilerek, PPAR agonistlerinin olası terapötik yararları üzerinde durulmuştur.

References

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The Role of Peroxisome Proliferator-Activated Receptors in the Pathogenesis of Insulin Resistance and Septic Shock

Year 2015, Volume: 5 Issue: 4, 247 - 258, 29.12.2015
https://doi.org/10.5455/musbed.20150715121617

Abstract

Peroxisome proliferator-activated receptors are ligand-activated transcription factors and they belong to class II nuclear receptor family. To date, three subspecies have been identified: peroxisome proliferator-activated receptor (PPAR) α, PPARβ and PPARγ. PPARα is mainly involved in the regulation of lipid metabolism and inflammatory processes. Since PPARβ is expressed in almost all tissues, the functional identity of it is not yet clear. PPARγ plays a key role in glucose homeostasis and the regulation of adipogenesis. Insulin resistance is attenuated biological response despite circulating normal or high levels of insulin in blood. In insulin resistance, the response caused by insulin isn’t sufficient or adequate at all tissues particularly in muscle, fat and liver. Development of insulin resistance is prevented by PPARα through regulation of genes affecting lipid metabolism and by PPARγ through provision of glucose homeostasis by different mechanisms. Sepsis is a systemic inflammatory response against a manifest or a potential infection; and septic shock is the severe form of sepsis that is accompanied by hypotension unresponsive to intravenous fluid administration. In preclinical studies proinflammatory gene expression was prevented by the inhibition of activation of transcription factors such as nuclear factor κB and activator protein-1 which are involved in the pathogenesis of sepsis and septic shock by PPAR agonists. This review focuses on the role of PPARs in the pathogenesis of insulin resistance and septic shock and discusses the potential therapeutic benefits of PPAR agonists.

References

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  • 17. Delerive P, Martin-Nizard F, Chinetti G, Trottein F, Fruchart JC, Najib J, Duriez P, Staels B. Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circ Res. 1999; 85: 394-402.
  • 18. Marx N, Sukhova GK, Collins T, Libby P, Plutzky J. PPARα activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation. 1999; 99: 3125- 3131.
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  • 20. Plutzky J. Macrovascular effects and safety issues of therapies for type 2 diabetes. Am J Cardiol. 2011; 108: 25B-32B.
  • 21. Plutzky J. The PPAR-RXR transcriptional complex in the vasculature: energy in the balance. Circ Res. 2011; 108: 1002-1016. 22. Oyekan A. PPARs and their effects on the cardiovascular system. Clin Exp Hypertens. 2011; 33: 287-293.
  • 23. Schultze AE, Alborn WE, Newton RK, Konrad RJ. Administration of a PPARalpha agonist increases serum apolipoprotein A-V levels and the apolipoprotein A-V/apolipoprotein C-III ratio. J Lipid Res. 2005; 46: 1591-1595.
  • 24. Schoonjans K, Staels B, Auwerx J. The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta. 1996; 1302: 93-109.
  • 25. Braissant O, Foufelle F, Scotto C, Dauca M, Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -β, and -gamma in the adult rat. Endocrinology. 1996; 137: 354-366.
  • 26. Rocchi S, Auwerx J. Peroxisome proliferator-activated receptor-gamma: a versatile metabolic regulator. Ann Med. 1999; 31: 342-351.
  • 27. Cefalu WT. Insulin resistance: cellular and clinical concepts. Exp Biol Med (Mywood). 2001; 226: 13-26.
  • 28. Kayaalp SO. Endokrin sistem farmakolojisi. Akılcıl Tedavi Yönünden Tıbbi Farmakoloji 1-2. 13. Baskı, Ankara: Pelikan Kitabevi; 2012. s. 1280. 29. DeFronzo RA. Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev. 1998; 5: 177-269.
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  • 31. Savage DV, Petersen KF, Shulman GI. Mechanisms of insulin resistance in humans and possible links with inflammation. Hypertension. 2005; 45: 828-833.
  • 32. Aygün G. Sepsis ve septik şok. Akılcı Antibiyotik Kullanımı ve Erişkinde Toplumdan Edinilmiş Enfeksiyonlar Sempozyum Dizisi. No: 31. 2002. 131-140.
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There are 76 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Review
Authors

Sefika Pinar Senol This is me

Bahar Tunctan This is me

Publication Date December 29, 2015
Submission Date February 16, 2015
Published in Issue Year 2015 Volume: 5 Issue: 4

Cite

APA Senol, S. P., & Tunctan, B. (2015). Peroksizom Proliferatör ile Etkinleştirilen Reseptörlerin İnsülin Direnci ve Septik Şok Patojenezindeki Rolü. Clinical and Experimental Health Sciences, 5(4), 247-258. https://doi.org/10.5455/musbed.20150715121617
AMA Senol SP, Tunctan B. Peroksizom Proliferatör ile Etkinleştirilen Reseptörlerin İnsülin Direnci ve Septik Şok Patojenezindeki Rolü. Clinical and Experimental Health Sciences. December 2015;5(4):247-258. doi:10.5455/musbed.20150715121617
Chicago Senol, Sefika Pinar, and Bahar Tunctan. “Peroksizom Proliferatör Ile Etkinleştirilen Reseptörlerin İnsülin Direnci Ve Septik Şok Patojenezindeki Rolü”. Clinical and Experimental Health Sciences 5, no. 4 (December 2015): 247-58. https://doi.org/10.5455/musbed.20150715121617.
EndNote Senol SP, Tunctan B (December 1, 2015) Peroksizom Proliferatör ile Etkinleştirilen Reseptörlerin İnsülin Direnci ve Septik Şok Patojenezindeki Rolü. Clinical and Experimental Health Sciences 5 4 247–258.
IEEE S. P. Senol and B. Tunctan, “Peroksizom Proliferatör ile Etkinleştirilen Reseptörlerin İnsülin Direnci ve Septik Şok Patojenezindeki Rolü”, Clinical and Experimental Health Sciences, vol. 5, no. 4, pp. 247–258, 2015, doi: 10.5455/musbed.20150715121617.
ISNAD Senol, Sefika Pinar - Tunctan, Bahar. “Peroksizom Proliferatör Ile Etkinleştirilen Reseptörlerin İnsülin Direnci Ve Septik Şok Patojenezindeki Rolü”. Clinical and Experimental Health Sciences 5/4 (December 2015), 247-258. https://doi.org/10.5455/musbed.20150715121617.
JAMA Senol SP, Tunctan B. Peroksizom Proliferatör ile Etkinleştirilen Reseptörlerin İnsülin Direnci ve Septik Şok Patojenezindeki Rolü. Clinical and Experimental Health Sciences. 2015;5:247–258.
MLA Senol, Sefika Pinar and Bahar Tunctan. “Peroksizom Proliferatör Ile Etkinleştirilen Reseptörlerin İnsülin Direnci Ve Septik Şok Patojenezindeki Rolü”. Clinical and Experimental Health Sciences, vol. 5, no. 4, 2015, pp. 247-58, doi:10.5455/musbed.20150715121617.
Vancouver Senol SP, Tunctan B. Peroksizom Proliferatör ile Etkinleştirilen Reseptörlerin İnsülin Direnci ve Septik Şok Patojenezindeki Rolü. Clinical and Experimental Health Sciences. 2015;5(4):247-58.

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