Sıçanlarda Streptozotosin ile İndüklenen Deneysel Diyabet Modelinde Hidroksitirosol’ün Pankreas Adacıklarında Speksin İmmünoreaktivitesi ve Serum İnsülin Düzeyleri Üzerine Etkisi

Year 2024, , 28 - 33, 25.06.2024

Tuba Yalçın , Sercan Kaya

https://doi.org/10.31196/huvfd.1410288

Abstract

Dünya çapında önemli bir sağlık sorunu olan diyabet (DM), pankreas adacıklarındaki β hücrelerinin kaybı ve insülin sekresyonunun azalmasıyla ilişkilidir. Hidroksitirosol (HxT), zeytinyağında yüksek konsantrasyonda bulunan bir fenoldür. Spexin (SPX), glikoz ve enerji gibi birçok metabolizmanın düzenlenmesinde rol oynar. Bu çalışma, sıçanlarda Streptozotosin ile indüklenen deneysel diyabet modelinde (eDM) HxT'nin dolaşımdaki insülin düzeyleri, pankreas adacıklarındaki histopatolojik değişiklikler ve SPX immünoreaktivitesi üzerindeki etkilerini belirlemeyi amaçladı.
Çalışmada kullanılan 32 adet sıçan, Kontrol, eDM, eDM+HxT ve HxT olmak üzere rastgele 4 gruba (n:8) ayrıldı. Deneyde tüm uygulamaların tamamlanmasıyla sakrifiye edilen sıçanların, kan ve pankreas dokuları alındı. Elde edilen serum örneklerinden insülin düzeyleri tespit edildi. Pankreas dokularında ise histopatolojik değişiklikler ve SPX immünreaktiviteleri değerlendirildi.
Serum insülin düzeyleri eDM’de azalırken pankreas adacıklarında histopatolojik değişiklikler artmıştı. Ayrıca eDM’de pankreas adacıklarında SPX immünreaktivitesi önemli ölçüde azalmıştı. Buna karşın HxT takviyesi (eDM+HxT grup), eDM’ye bağlı olumsuzlukları düzenleyebildi.
DM’de HxT takviyesi iyileştirici ve tedavi edici etki gösterebilir. SPX, pankreasın endokrin fonksiyonlarını düzenlemede etkili olabilir.

Keywords

Diyabet, Hidroksitirozol, Pankreas, Spexin, Streptozotosin

Ethical Statement

Bu çalışma Fırat Üniversitesi Hayvan Deneyleri Etik Kurulunun 13/11/2023-19739 tarihli onayı ile yapılmıştır.

Supporting Institution

Batman Üniversitesi Bilimsel Araştırma Projeleri

Project Number

BTÜBAP-2023-SHMYO-02

Thanks

Batman Üniversitesi Bilimsel Araştırma Projeleri birimine teşekkür ederiz.

The effect of Hydroxytyrosol on Spexin immunoreactivity in pancreatic islets and serum insulin levels in a Streptozotocin-induced experimental diabetes model in rats

Abstract

Diabetes (DM), a major health problem worldwide, is associated with the loss of β cells in the pancreatic islets and decreased insulin secretion. Hydroxytyrosol (HxT) is a phenol found in high concentrations in olive oil. Spexin (SPX) plays a role in regulating many metabolisms such as glucose and energy. This study aimed to determine the effects of HxT on circulating insulin levels, histopathological changes in pancreatic islets, and SPX immunoreactivity in a Streptozotocin-induced experimental diabetes model (eDM) in rats.
The 32 male rats used in the study were randomly divided into 4 groups (n: 8): Control, eDM, eDM+HxT, and HxT. After completing all applications in the experiment, the blood and pancreas tissues of the sacrificed rats were taken. Insulin levels were determined from the serum samples obtained. Histopathological changes and SPX immunoreactivities were evaluated in pancreatic tissues.
While serum insulin levels decreased in eDM, histopathological changes in pancreatic islets increased. Additionally, SPX immunoreactivity in pancreatic islets was significantly reduced in eDM. On the other hand, HxT supplementation (eDM+HxT group) regulated eDM-related adverse effects.
While HxT supplementation may have a curative and therapeutic effect in DM, it was concluded that SPX may be effective in regulating the endocrine functions of the pancreas.

Keywords

Diabetes, Hydroxytyrosol, Pancreas, Spexin, Streptozotocin

Ethical Statement

This study was conducted with the approval of the Fırat University Animal Experiments Ethics Committee dated 13/11/2023-19739.

Supporting Institution

Batman University Scientific Research Projects

Project Number

BTÜBAP-2023-SHMYO-02

References

• Adeghate E, D'Souza C, Ali II, Saeed Z, Alharthi SH, Alhadhrami ZK, & Tariq S, 2022: Spexin co-localizes with insulin in pancreatic islet cells of normal and diabetic rats. The FASEB J, 36 (1).
• Alkhatib A, Tsang C, Tuomilehto J, 2018: Olive oil nutraceuticals in the prevention and management of diabetes: From molecules to lifestyle. Int J Mol Sci, 19 (7), 2-15.
• Auñon-Calles D, Canut L, Visioli F, 2013: Toxicological evaluation of pure hydroxytyrosol. Food Chem Toxicol, 55, 498-504.
• Bertelli M, Kiani AK, Paolacci S, Manara E, Kurti D, Dhuli K, Michelini S, 2020: Hydroxytyrosol: A natural compound with promising pharmacological activities. J Biotechnol, 10 (309), 29-33.
• Binou P, Stergiou A, Kosta O, Tentolouris N, Karathanos VT, 2023: Positive contribution of hydroxytyrosol-enriched wheat bread to HbA1c levels, lipid profile, markers of inflammation, and body weight in subjects with overweight/obesity and type 2 diabetes mellitus. Eur J Nutr, 62 (5), 2165-2176.
• Chandramohan R, Saravanan S, Pari L, 2017: Beneficial effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats. Pharm Biol, 55 (1), 1631–7.
• Dai J, Ni Y, Wu D, Jiang Y, Jin S, Zhang S, Liu R, 2023: Circulating spexin levels are influenced by the glycemic status and correlated with pancreatic β-cell function in Chinese subjects. Acta Diabetol, 60 (2), 305-313.
• Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Martínez-González MA, 2018: Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med, 21, 378 (25), e34.
• Gallagher DM, O’Harte FP, Irwin N, 2024: An update on galanin and spexin and their potential for the treatment of type 2 diabetes and related metabolic disorders. Peptides,171, 171096.
• Gowdu T, Dayanand CD, 2021: Spexin in metabolic syndrome-an overview. SAS J Med, 7, 15-25.
• Gu L, Yan S, Huang Y, Yang J, Peng Y, Wang Y, 2022: Serum spexin differed in newly diagnosed type 2 diabetes patients according to body mass index and increased with the improvement of metabolic status. Front Endocrinol (Lausanne), 13, 1086497.
• Hamden K, Allouche N, Damak M, and Elfeki A, 2009: Hypoglycemic and antioxidant effects of phenolic extracts and purified hydroxytyrosol from olive mill waste in vitro and rats. Chem Biol Interact, 14, 180 (3), 421-32.
• Jafari-Rastegar N, Hosseininia HS, Jalilvand E, Naseroleslami M, Khakpai F, Mousavi-Niri N, 2023: Oral administration of nano-tyrosol reversed the diabetes-induced liver damage in streptozotocin-induced diabetic rats. J Diabetes Metab Disord, 22 (1), 297-305.
• Kaya S, 2023a: Speksin'in metabolizmayı düzenlemedeki potansiyel rolü. Internatıonal Congress on Health Scıences and Technologıes Research Anatolia, Ankara, Turkey, 6-8.
• Kaya S, 2023b: The effect of n-acetylcysteine administration on trpm2 ion channels in aluminum chloride-induced cardiotoxic rat model. FÜ Sağ Bil Tıp Derg, 37 (2), 105 – 112.
• Kaya S, Yalçın T, Boydak M, Dönmez HH, 2023: Protective effect of N-acetylcysteine against aluminum-induced kidney tissue damage in rats. Biol Trace Elem Res, 201 (4), 1806-1815.
• Lee H, Im SW, Jung CH, Jang YJ, Ha TY, Ahn J, 2016: Tyrosol, an olive oil polyphenol, inhibits ER stress-induced apoptosis in pancreatic β-cell through JNK signaling. Biochem Biophys Res Commun, 469 (3), 748-752.
• Lenzen S, 2008: The mechanisms of alloxan-and streptozotocin-induced diabetes. Diabetologia, 51 (2), 216-26. Lv SY, Zhou YC, Zhang XM, Chen WD, Wang YD, 2019: Emerging roles of NPQ/spexin in physiology and pathology. Front Pharmacol, 10, 457.
• Lytrivi M, Castell AL, Poitout V, Cnop M, 2020: Recent insights into mechanisms of β-cell lipo-and glucolipotoxicity in type 2 diabetes. J Mol Biol, 6, 432 (5), 1514-1534.
• Marrano N, Spagnuolo R, Biondi G, Cignarelli A, Perrini S, Vincenti L, Natalicchio A, 2021:Effects of extra virgin olive oil polyphenols on beta-cell function and survival. Plants (Basel), 3, 10 (2), 286.
• Rodríguez-Pérez MD, Pérez de Algaba I, Martín-Aurioles E, Arrebola MM, Ortega-Hombrados L, Verdugo C., González-Correa JA, 2022: Neuroprotective Effect of 3′, 4′-Dihydroxyphenylglycol in Type-1-like Diabetic Rats—Influence of the Hydroxytyrosol/3′, 4′-dihydroxyphenylglycol Ratio. Nutrients, 14 (6), 1146.
• Rodriguez-Pérez MD, Santiago-Corral L, Ortega-Hombrados L, Verdugo C, Arrebola MM, Martín-Aurioles E, González-Correa JA, 2023: The Effect of the Extra Virgin Olive Oil Minor Phenolic Compound 3′, 4′-Dihydroxyphenylglycol in Experimental Diabetic Kidney Disease. Nutrients, 15 (2), 377.
• Sassek M, Kolodziejski PA, Szczepankiewicz D, and Pruszynska-Oszmalek E, 2019: Spexin in the physiology of pancreatic islets—mutual interactions with insulin. Endocrine, 63, 513-519.
• Soylu H, Karacor K, 2023: The effects of hydroxytyrosol on Prdx6 and insulin expression in diabetic rat pancreases. Histochem Cell Biol,160 (2), 127-134.
• Sukanya V, Pandiyan V, Vijayarani K, Padmanath K, 2020: A study on insulin levels and the expression of glut 4 in streptozotocin (STZ) induced diabetic rats treated with mustard oil diet. Indian J Clin Biochem, 35, 488–496.
• Uyar A, Abdulrahman NT, 2020: A histopathological, immunohistochemical and biochemical investigation of the antidiabetic effects of the Pistacia terebinthus in diabetic rats. Biotech Histochem, 95 (2), 92-104.
• Vlavcheski F, Young M, Tsiani E, 2019: Antidiabetic effects of hydroxytyrosol: In vitro and in vivo evidence. Antioxidants, 8 (6), 188.
• Wang L, Tran A, Lee J, Belsham DD, 2020: Palmitate differentially regulates Spexin, and its receptors Galr2 and Galr3, in GnRH neurons through mechanisms involving PKC, MAPKs, and TLR4. Mol Cell Endocrinol, 518, 110991.
• Wang N, Liu Y, Ma Y, Wen D, 2018: Hydroxytyrosol ameliorates insulin resistance by modulating endoplasmic reticulum stress and prevents hepatic steatosis in diet-induced obesity mice. J Nutr Biochem, 57, 180-188.
• Wani TA, Masoodi FA, Gani A, Baba WN, Rahmanian N, Akhter R, Ahmad M, 2018: Olive oil and its principal bioactive compound: Hydroxytyrosol–A review of the recent literature. Trends Food Sci Technol, 77, 77-90.
• Xie YD, Chen ZZ, Shao LH, Wang QT, Li N, Lu WF, Bian XL, 2018: A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic, antioxidant, and hepatoprotective effects. Bioorg Med Chem Lett, 1, 28 (18), 3119-3122.
• Yalcin T, Kuloglu T, Kaya Tektemur N, Tektemur A, Ozan İE, 2024: Effects of N-acetylcysteine on spexin immunoreactivity in kidney tissues of rats treated with adriamycin. Iran J Basic Med Sci, 27, 233-240.