Tip 2 diyabetli hastalarda angiopoietin benzeri protein 8 (ANGPTL8) ve Alarin düzeylerinin karşılaştırmalı bir değerlendirmesi

Year 2022, Volume: 47 Issue: 2, 589 - 595, 30.06.2022

Mustafa Timurkaan , Hakan Ayyıldız

https://doi.org/10.17826/cumj.1038569

Abstract

Amaç: Tip 2 Diabetes Mellitus (T2DM), dünya çapında milyonlarca insanı etkileyen en ciddi halk sağlığı sorunlarından biridir. Dünyada diyabet teşhisi konan 537 milyon yetişkin mevcuttur ve bu yetişkinlerin yaklaşık %90'ı tip 2 diyabet hastasıdır. Çalışmamızda T2DM tanısı alan hastaların angiopoietin benzeri protein 8 (ANGPTL8) ve alarin düzeylerini kendi aralarında ve sağlıklı kontrol grubu ile karşılaştırmalı olarak inceledik.
Gereç ve Yöntem: Çalışmamız yeni T2DM tanısı almış ve herhangi bir ilaç kullanmayan 67 hastadan oluşan diyabet grubu ve 55 sağlıklı kişiden oluşan kontrol grubu ile yapıldı. ANGPTL8 ve Alarin seviyeleri ELISA (enzyme-linked immunosorbent assay) yöntemi kullanılarak ölçüldü.
Bulgular: Kontrol grubuna kıyasla diyabetik grupta Alarin ve ANGPTL8 düzeylerinde anlamlı bir artış bulduk. Hasta grubunda alarin düzeyleri ile ANGPTL8, trigliserit ve insülin düzeyleri arasında pozitif bir ilişki bulunmuştur. Ayrıca hasta grubunda erkeklerde her iki adipokin düzeyi daha yüksek iken, kontrol grubunda erkeklerde her iki adipokin düzeyinin kadınlara göre daha düşük olduğu ve ANGPTL8 düzeylerinde anlamlı farklılık olduğu sonucuna vardık.
Sonuç: Yüksek ANGPTL8 ve Alarin düzeylerinin insülin direnci yolu ile diyabet gelişimini kolaylaştırabileceği düşünülmüştür. Bu mekanizma daha net bir şekilde aydınlatılırsa diyabetik tedavi projeksiyonunda önemli bir iyileşme olabilir.

Keywords

ANGPTL8, Alarin, Diabetes Mellitus, Adipokines

Supporting Institution

herhangi bir kurum tarafından desteklenmemiştir.

A comparative evaluation of the angiopoietin-like protein 8 (ANGPTL8) and alarin levels in patients with type 2 diabetes mellitus

Abstract

Purpose: Type 2 Diabetes Mellitus (T2DM) is one of the most serious public health problems that affect millions of people worldwide. There are 537 million adults diagnosed with diabetes worldwide and approximately 90% of these adults have type 2 diabetes. The study examined angiopoietin-like protein 8 (ANGPTL8) and Alarin levels of the patients diagnosed with T2DM in comparison with each other and with the healthy control group.
Materials and Methods: The study was conducted with a diabetes group consisting of 67 patients who were newly diagnosed with T2DM and who did not use any medication, and the control group consisting of 55 healthy people. ANGPTL8 and Alarin levels were measured using the ELISA (enzyme-linked immunosorbent assay) method.
Results: We found a significant increase in alarin and ANGPTL8 levels in the diabetic group compared to the control group. Furthermore, a positive correlation between Alarin levels and ANGPTL8, triglyceride, and insulin levels was found in the patient group. In addition, while both adipokines were higher in males in the patient group, both adipokines levels were lower in males than females in the control group, and there was a significant difference in ANGPTL8 levels.
Conclusion: High levels of ANGPTL8 and Alarin may facilitate the development of diabetes through the insulin resistance pathway. If this mechanism is more clearly elucidated, there may be a significant improvement in diabetic treatment projection.

Keywords

ANGPTL8, alarin, diabetes mellitus, adipokines

References

• Rosen ED, Kaestner KH, Natarajan R, Patti ME, Sallari R, Sander M et al. Epigenetics and epigenomics: Implications for diabetes and obesity. Diabetes. 2018;67:1923–1931.
• IDF Diabetes Atlas 2021. 10th Edition. https://www.idf.org/news/240:diabetes-now-affects-one-in-10-adults-worldwide.html (accessed Feb 2022).
• Wilcox G. Insulin and insulin resistance. Clin Biochem Rev. 2005;26:19-39.
• Samuel VT, Shulman GI. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest. 2016;126:12-22.
• Ren G, Kim JY, Smas CM. Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism. Am J Physiol Endocrinol Metab. 2012;303:334-351
• Zhang R. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. Biochem Biophys Res Commun. 2012;424:786-92.
• Quagliarini F, Wang Y, Kozlitina J, Grishin NV, Hyde R, Boerwinkle E et al. Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci U S A. 2012;109:19751-6.
• Yi P, Park JS, Melton DA. Betatrophin: a hormone that controls pancreatic beta cell proliferation. Cell. 2013;153:747–758.
• Santic R, Fenninger K, Graf K, Schneider R, Hauser KC, Schilling FH et al. Gangliocytes in neuroblastic tumors express alarin, a novel peptide derived by differential splicing of the galanin-like peptide gene. J Mol Neurosci. 2006;29:145-152.
• Santic R, Schmidhuber SM, Lang R, Rauch I, Voglas E, Eberhard N et al. Alarin is a vasoactive peptide. Proc Natl Acad Sci U S A. 2007;104,10217–10222.
• Guo L, Shi M, Zhang L, Shao H, Fang P, Ma Y et al. Galanin antagonist increases insulin resistance by reducing glucose transporter 4 effect in adipocytes of rats. Gen Comp Endocrinol. 2012;173:159–163.
• Liang Y, Sheng S, Fang P, Ma Y, Li J, Shi Q et al. Exercise-induced galanin release facilitated GLUT4 translocation in adipocytes of type 2 diabetic rats. Pharmacol Biochem Behav. 2012;100:554–559.
• Zhang Z, Sheng S, Guo L, Li G, Zhang L, Zhang L et al. Intracerebroventricular administration of galanin antagonist sustains insulin resistance in adipocytes of type 2 diabetic trained rats. Mol Cell Endocrinol. 2012;361:213–218.
• DeFronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773–795.
• Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860–867.
• MacDougald OA, Burant CF. The rapidly expanding family of adipokines. Cell Metab. 2007;6:159–161.
• Abu-Farha M, Al-Khairi I, Cherian P, Chandy B, Sriraman D, Alhubail A et al. Increased ANGPTL3, 4 and ANGPTL8/betatrophin expression levels in obesity and T2D. Lipids Health Dis. 2016;15:181.
• Gusarova V, Alexa CA, Na E, Stevis PE, Xin Y, Bonner-Weir S et al. ANGPTL8/betatrophin does not control pancreatic beta cell expansion. Cell. 2014;159:691–696.
• Cox AR, Lam CJ, Bonnyman CW, Chavez J, Rios JS, Kushner JA. Angiopoietin-like protein 8 (ANGPTL8) / betatrophin overexpression does not increase beta cell proliferation in mice. Diabetologia. 2015;58:1523–1531.
• Yi M, Chen RP, Yang R, Guo XF, Zhang JC, Chen H. Betatrophin Acts as a Diagnostic biomarker in type 2 diabetes mellitus and is negatively associated with HDL-Cholesterol. Int J Endocrinol. 2015;2015:479157.
• Yamada H, Saito T, Aoki A, Asano T, Yoshida M, Ikoma A et al. Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes. Endocr J. 2015;62:417–21.
• Chen X, Lu P, He W, Zhang J, Liu L, Yang Y et al. Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resistance. J Clin Endocrinol Metab. 2015; 100:96-100.
• Gao T, Jin K, Chen P, Jin H, Yang L, Xie X et al. Circulating betatrophin correlates with triglycerides and postprandial glucose among different glucose tolerance statuses – a case-control study. PLoS One. 2015;10:0133640.
• Abu-Farha M, Abubaker J, Noronha F, Al-Khairi I, Cherian P, Alarouj M et al. Lack of associations between betatrophin/ANGPTL8 level and C-peptide in type 2 diabetic subjects. Cardiovasc Diabetol. 2015;14:112.
• Fenzl A, Itariu BK, Kosi L, Fritzer-Szekeres M, Kautzky-Willer A, Stulnig TM et al. Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals. Diabetologia. 2014;57:1204-8.
• Guo K, Lu J, Yu H, Zhao F, Pan P, Zhang L et al. Serum betatrophin concentrations are significantly increased in overweight but not in obese or type 2 diabetic individuals. Obesity. 2015;23:793-7.
• Gomez-Ambrosi J, Pascual E, Catalan V, Rodriguez A, Ramirez B, Silva C et al. Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes. J Clin Endocrinol Metab. 2014;99:2004–9.
• Fu Z, Berhane F, Fite A, Seyoum B, Abou-Samra AB, Zhang R. Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity. Sci Rep. 2014;4:5013.
• Zhang Z, Wu Y, Sheng S, Guo L, He B, Fang P et al. Intracerebroventricular injection of alarin increased glucose uptake in skeletal muscle of diabetic rats. PLoS One. 2015;10:0139327
• Guo L, Fang P, Yu M, Shi M, Bo P, Zhang Z. Central alarin ameliorated insulin resistance of adipocytes in type 2 diabetic rats. J Endocrinol. 2014;223:217-25.
• Mikó A, Füredi N, Tenk J, Rostás I, Soós S, Solymár M et al. Acute central effects of alarin on the regulation on energy homeostasis. Neuropeptides. 2017;64:117-122.
• Hu W, Fan X, Zhou B, Li L, Tian B, Fang X et al. Circulating alarin concentrations are high in patients with type 2 diabetes and increased by glucagon-like peptide-1 receptor agonist treatment. Medicine. 2019;98:16428.
• Zhou X, Luo M, Zhou S, Cheng Z, Chen Z, Yu X. Plasma alarin level and its influencing factors in obese newly diagnosed type 2 diabetes patients. Diabetes Metab Syndr Obes. 2021;14:379.
• Kilinc F, Demircan F, Gozel N, Onalan E, Karatas A, Pekkolay Z et al. Assessment of serum alarin levels in patients with type 2 diabetes mellitus. Acta Endocrinol (Buchar). 2020;16:165.
• Fraley GS, Leathley E, Lundy N, Chheng E, King I, Kofler B. Effects of alarin on food intake, body weight and luteinizing hormone secretion in male mice. Neuropeptides. 2012;46:99–104.