Sağlıklı insanlarda uyku yoksunluğunun insülin, resistin ve visfatin düzeylerine etkileri

Sağlıklı İnsanlarda Uyku Yoksunluğunun İnsülin, Resistin ve Visfatin Düzeylerine Etkileri ÖZ Giriş: Uyku yoksunluğunun, dolaşımdaki insülin ve glikoz seviyelerini etkilediği ve bu durumun glikoz metabolizmasını modüle ettiği bilinmektedir. Bununla birlikte, uyku yoksunluğu sırasında glikoz homeostazındaki değişikliklerin mekanizması bilinmemektedir. Bu çalışmada, yukarıda belirtilen mekanizmaya ışık tutmak için dolaşımdaki resistin ve visfatin düzeylerini 40 saatlik uyku kaybına yanıt olarak araştırdık. Metot: Bu çalışmada 12 sağlıklı genç yetişkin (18-32 yaş arası) yer aldı. Tüm katılımcılara polisomnografik değerlendirme ve oral glukoz tolerans testi uygulandı, ardından sabah saatlerinde açlık venöz kan örnekleri alındı. Daha sonra katılımcılar, aktigrafik izleme altında 40 saat uyanık kaldılar. Uyku yoksunluğunun sonunda tekrar kan örnekleri alındı. Tüm kan örneklerinde serum insülin, resistin ile visfatin düzeyleri ölçüldü. İnsülin kimyasal immün assay metodu ile belirlenirken, resistin ve visfatin seviyeleri ELISA ile tahlil edildi. Bulgular: Başlangıç durumuna kıyasla, 40 saatlik toplam uyku yoksunluğu serum insülin seviyelerinde (10,75 ± 7,75 ve 35,98 ± 27,96 IU; p = 0,002) anlamlı artış ve resistin seviyelerinde (21,94 ± 7,65 ve 11,71 ± 5,31 IU; p = 0,002) anlamlı azalma gözlenmiştir. Visfatin seviyelerinde anlamlı değişim gözlenmemiştir (6,29 ± 3,31 ve 5,43 ± 5,08 IU; p> 0,05). Sonuç: Bu sonuçlar, kısa süreli toplam uyku yoksunluğunun, resistinden bağımsız şekilde, yüksek insülin düzeyleri ile kanıtlanan, insülin direncine yol açabileceğini düşündürmektedir. Bu durum kronik uyku yoksunluğu koşulları altında tip 2 diabetes mellitusun patofizyolojisine katkıda bulunabilir.

Anahtar Kelimeler:

Uyku yoksunluğu, Resistin, Visfatin, İnsulin

The effects of sleep deprivation on insulin, resistin and visfatin levels in healthy humans

The Effects of Sleep Deprivation on Insulin, Resistin and Visfatin Levels in Healthy Humans ABSTRACT Background: Sleep deprivation is known to affect circulating insulin and glucose levels which in turn modulate glucose metabolism. However, the mechanism of alterations in glucose homeostasis during sleep deprivation is not known. In this study, we investigated circulating resistin and visfatin levels in response to 40 hours of sleep loss in order to shed light on the above-mentioned mechanism. Methods: This study included 12 healthy young adult subjects (aged between 18-32 years). All participants underwent polysomnographic evaluation and oral glucose tolerance test and then fasting venous blood samples were collected in morning hours. Then, subjects remained awake for 40 hours under actigraphic monitorization. At the end of sleep deprivation, blood samples were collected again. Serum insulin, resistin and visfatin levels were measured in all blood samples. Insulin was determined by chemical immune assay method, whereas resistin and visfatin levels assayed by ELISA. Results: Compared to baseline, 40-hour total sleep deprivation resulted in a significant increase in serum insulin levels (10.75±7.75 vs 35.98±27.96 IU; p=0.002) and a significant decrease in resistin levels (21.94±7.65 vs 11.71±5.31 IU; p=0.002). Visfatin levels remained unchanged (6.29±3.31 vs 5.43±5.08 IU; p>0.05). Conclusion: These results suggested that short-term total sleep deprivation may lead to insulin resistance which was evidenced by a significant increase insulin levels independent of resistin. This may contribute to pathophysiology of type 2 diabetes mellitus under conditions of chronic sleep deprivation.

Keywords:

Sleep deprivation, Resistin, Visfatin, İnsulin,

PDF

___

REFERENCES 1. Van Cauter E, Spiegel K, Tasali E, Leproult R. Metabolic consequences of sleep and sleep loss. Sleep Med. 2008;9(Suppl.1):S23-S28.
2. Gottlieb DJ, Punjabi NM, Newman AB, Resnick HE, Redline S, Baldwin CM, Nieto FJ. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med. 2005;165:863-868.
3. Deng H, Tam T, Zee BC, Chung RY, Su X, Jin L, Chan T, Chang L, Yeoh E, Lao XQ. Short sleep duration increases metabolic impact in healthy adults: a populationbased cohort study. Sleep. 2017;40(10).
4. Brzecka A, Natalia M, Nikolenko VN, Ashraf GM, Ejma M, Leszek J, Daroszevski C, Sarul K, Mikhaleva LM, Somasundaram SG, Kirkland CE, Bachurin SO, Aliev G. Sleep disturbances and cognitive impairment in the course of type 2 diabetes-a possible link. Curr Neuropharmacol. 2021;19:78-9.
5. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354: 1435–1439.
6. Hayes AL, Xu F, Babineau D, Patel SJ. Sleep duration and circulating adipokine levels. Sleep. 2011;34(2):147-152.
7. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature. 2001;409(6818):307-312.
8. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I. Visfatin: A protein secreted by visceral fat that mimics the effects of insulin. Science. 2005;307(5708):426-430.
9. McGee KC, Harte AL, da Silva NF, Al-Daghri N, Creely SJ, Kusminski CM, Tripathi G, Levick PL, Khanolkar M, Evans M, Chittari MV, Patel V, Kumar S, Mc Ternan PG. Visfatin is regulated by rosiglitazone in type 2 diabetes mellitus and influenced by NFkappa B and JNK in human abdominal subcutaneous adipocytes. PLoS One. 2011;6:e20287.
10. Gökçel A, Baltalı M, Tarım E, Bağış T, Gümürdülü Y, Karaköse H, Yalçın F, Akbaba M, Güvener N. Detection of insulin resistance in Turkish adults: a hospital-based study. Diabetes Obes Metab. 2003;5(2):126-30.
11. Kamba A, Daimon M, Murakami H, Otaka H, Matsuki K, Sato E, Tanabe J, Takayasu S, Matsuhashi Y, Yanagimachi M, Terui K, Kageyama K, Tokuda I, Takahashi I, Nakaji S. Association between higher serum cortisol levels and decreased insulin secretion in a general population. PLoS ONE. 2016;11(11):e0166077.
12. Alwashih MA, Stimson RH, Andrew R, Walker BR, Watson DG. Acute interaction between hydrocortisone and insulin alters the plasma metabolome in humans. Sci Rep. 2017;7(1):11488.
13. Öztürk L, Pelin Z, Karadeniz D, Kaynak H, Çakar L, Gözükırmızı E. Effects of 48 hours sleep deprivation on human immune profile. Sleep Res Online. 1999;2(4):107-11.
14. Heo YJ, Choi S, Jeon JY, Han SJ, Kim DJ, Kang Y, Lee KW, Kim HJ. Visfatin induces inflammation and insulin resistance via the NF-kB and STAT3 signaling pathways in hepatocytes. J Diabetes Res. 2019;4021623:1-11.
15. Skop V, Kontrova K, Zidek V, Pravenec V, Kazdova L, Mikulik K, Sajdok J, Zidkova J. Autocrine effects of visfatin on hepatocyte sensitivity to insulin action. Physiol Res. 2010; 59:615-8.
16. Revollo JR, Korner A, Mills KF, Satoh A, Wang T, Garten A, Dasgupta B, Sasaki Y, Wolberger C, Townsend RR, Milbrandt J, Kiess W, Imai SI. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosyntetic enzyme. Cell Metab. 2007;6:363-75.
17. Nourbakhsi M, Nourbakhsh M, Gholinejad Z, Razzaghy-Azar M. Visfatin in obese children and adolescents and its asoociation with insulin resistance and metabolic syndrome. Scand J Clin & Lab Invest. 2015;75:183-88.
18. Su K, Li Y, Zhang D, Yuan J, Zhang C, Liu Y, Song L, Lin Q, Li M, Dong J. Relation of circulating resistin to insulin resistance in type 2 diabetes and obesity: a systematic review and meta-analysis. Front Physiol. 2019;10:1399.
19. Kaser S, Kaser A, Sandhofer A, Ebenbichler CF, Tilg H, Patsch JR. Resistin Messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem Biophys Res Commun. 2003;309:286-90.