TİP 1 DİYABETES MELLİTUS OLUŞTURULAN SIÇANLARIN BEYNİNDE LEPTİN MİKTARI AZALMAKTADIR

Yıl 2019, Cilt 20, Sayı 2, 91 - 97, 29.04.2019

Erhan ŞAHİN Öykü ÖZCAN Ezgi BEKTUR Cengiz BAYÇU Ümide ÖZKAY DEMİR Özgür Devrim CAN Varol ŞAHİNTÜRK

https://doi.org/10.18229/kocatepetip.408118

Öz

AMAÇ: Leptin hormonu, iştah ve vücut metabolizmasının düzenlenmesinde önemli görevler üstlenmekte ve başlıca yağ dokusunda sentezlenmektedir. Leptinin yağ dokuda sentezlendikten sonra koroid pleksus aracılığı ile beyne taşındığı bilinmektedir. Bu çalışmanın amacı Tip 1 diyabetes mellitus oluşturulan sıçanların beyninde leptin ifadesinin ve miktarının araştırılmasıdır.

GEREÇ VE YÖNTEM: Çalışmamızda toplam 14 adet yetişkin, erkek Wistar Albino sıçan 2 eşit gruba ayrıldı (n=7). Kontrol grubuna hiçbir uygulama yapılmadı. Diyabetes mellitus grubundaki hayvanlara ise tek doz (55 mg/kg) streptozotosin intraperitoneal olarak verildi ve kan glukoz seviyesi >280 mg/dL ölçüldüğünde Tip 1diyabetes mellitus geliştiği kabul edildi. Deney sonunda alınan beyin örnekleri %10’luk formaldehit ile fikse edildikten sonra rutin doku takip işleminin ardından alınan kesitlere leptin immünohistokimyasal boyaması uygulandı. Beyin dokularında western blot yöntemi ile leptin miktarına bakıldı.

BULGULAR: Tüm gruplara ait beyin kesitlerinde sadece koroid pleksusta leptin boyanması saptandı. Buna göre, leptin boyanmasının Tip 1 diyabetes mellitus geliştirilen sıçanlarda azaldığı saptandı. Western blot ile Tip 1 diyabetes mellitus grubunda leptin miktarının belirgin olarak azaldığı saptandı.

SONUÇ: Bu çalışmayla tokluk hissini oluşturmak üzere koroid pleksus üzerinden beyne geçen leptin hormonu ile diyabet arasında yakın bir ilişki olduğu ve bu hormonun diyabetle azaldığı gösterilmiştir. Bu çalışmadan yola çıkarak Tip 1 diyabet ve leptin hormonu ilişkisi derinlemesine irdelenmelidir.

Anahtar Kelimeler

Diyabetes mellitus, beyin, leptin, koroid pleksus

LEPTIN QUANTITY DECREASES İN TYPE 1 DIABETES MELLITUS INDUCUED RATS BRAIN

Öz

OBJECTIVE: Leptin hormone plays an important role in regulation of appetite and body metabolism and is mainly synthesized in fat tissue. It is known that leptin is transported to the brain via choroid plexus after synthesized in the fat tissue. The aim of this study is to investigate the amount and expression of leptin in the brain of rats with type 1 diabetes mellitus.

MATERIAL AND METHODS: A total of 14 adult male Wistar Albino rats were divided into 2 equal groups (n = 7). No application was made to the control group. A single dose (55 mg/kg) of streptozotocin was administered intraperitoneally to the animals of the diabetes mellitus group and it was considered that type 1 diabetes mellitus developed when blood glucose level > 280 mg/dL. Brain samples taken at the end of the experiment were fixed with %10 formaldehyde and then subjected to routine tissue monitoring followed by leptin immunohistochemical staining. The amount of leptin was determined by western blotting in brain tissues.

RESULTS: In all groups leptin staining was detected only in the choroid plexus of rat brains. According to this knowlodge, it was determined that leptin staining decreased in type 1 diabetes mellitus developed rats. The decreased leptin in the type 1 diabetes mellitus group was showed by western blot too.

CONCLUSIONS: Type 1 diabetes reduces the expression and amount of leptin in the choroid plexus.

Anahtar Kelimeler

Diabetes mellitus, brain, leptin, choroid plexus

Kaynakça

• Klok M, Jakobsdottir S, Drent M. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obesity reviews. 2007;8(1):21-34.
• Fantuzzi G, Faggioni R. Leptin in the regulation of immunity, inflammation, and hematopoiesis. Journal of leukocyte biology. 2000;68(4):437-446.
• Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, et al. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002;111(3):305-317.
• Shintani M, Ogawa Y, Ebihara K, Aizawa-Abe M, Miyanaga F, Takaya K, et al. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes. 2001;50(2):227-232.
• Lin S, Storlien LH, Huang X-F. Leptin receptor, NPY, POMC mRNA expression in the diet-induced obese mouse brain. Brain research. 2000;875(1):89-95.
• Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science-AAAS-Weekly Paper Edition. 1995;269(5223):543-545.
• Abac A, Böber E, Büyükgebiz A. Tip 1 Diyabet. Güncel Pediatri 2007;5:1-10.
• Geyikli İ, Keskin M, Kör Y, Akan M. Increased resistin serum concentrations in patients with type 1 diabetes mellitus. Journal of clinical research in pediatric endocrinology. 2013;5(3):189.
• Ismail MM, Abdel Hamid TA, Ibrahim AA, Marzouk H. Serum adipokines and vitamin D levels in patients with type 1 diabetes mellitus. Archives of medical science : AMS. 2017;13(4):738-744.
• Kratzsch J, Deimel A, Galler A, Kapellen T, Klinghammer A, Kiess W. Increased serum soluble leptin receptor levels in children and adolescents with type 1 diabetes mellitus. European journal of endocrinology. 2004;151(4):475-481.
• Kurçer Z, Karaoğlu D. Deneysel Diyabet Modellerinde Alloksan ve Streptozotosin Kullanımı. Turkish Journal of Endocrinology & Metabolism. 2012;16(2).34-40
• Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL. Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia. 2012;83(4):650-659.
• Masuzaki H, Ogawa Y, Aizawa-Abe M, Hosoda K, Suga J, Ebihara K, et al. Glucose metabolism and insulin sensitivity in transgenic mice overexpressing leptin with lethal yellow agouti mutation: usefulness of leptin for the treatment of obesity-associated diabetes. Diabetes. 1999;48(8):1615-1622.
• Barr VA, Malide D, Zarnowski MJ, Taylor SI, Cushman SW. Insulin stimulates both leptin secretion and production by rat white adipose tissue. Endocrinology. 1997;138(10):4463-4472.
• Bradley RL, Cheatham B. Regulation of ob gene expression and leptin secretion by insulin and dexamethasone in rat adipocytes. Diabetes. 1999;48(2):272-278.
• Tsubai T, Noda Y, Ito K, Nakao M, Seino Y, Oiso Y, et al. Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose. Heliyon. 2016;2(11):e00194.
• Banks WA, Kastin AJ, Huang W, Jaspan JB, Maness LM. Leptin enters the brain by a saturable system independent of insulin. Peptides. 1996;17(2):305-311.
• Zlokovic BV, Jovanovic S, Miao W, Samara S, Verma S, Farrell CL. Differential regulation of leptin transport by the choroid plexus and blood-brain barrier and high affinity transport systems for entry into hypothalamus and across the blood-cerebrospinal fluid barrier. Endocrinology. 2000;141(4):1434-1441.
• Di Spiezio A, Sandin ES, Dore R, Müller-Fielitz H, Storck SE, Bernau M, et al. The LepR-mediated leptin transport across brain barriers controls food reward. Molecular metabolism. 2018;(8):13-22.
• Wang Y, Ali Y, Lim C-Y, Hong W, Pang ZP, Han W. Insulin-stimulated leptin secretion requires calcium and PI3K/Akt activation. Biochemical Journal. 2014;458(3):491-498.
• Kang S-J, Kim J-H, Gang Z, Yook Y-S, Yoon J-R, Ha G-C, et al. Effects of 12-week circuit exercise program on obesity index, appetite regulating hormones, and insulin resistance in middle-aged obese females. Journal of physical therapy science. 2018;30(1):169-173.
• Mueller WM, Gregoire FM, Stanhope KL, Mobbs CV, Mizuno TM, Warden CH, et al. Evidence that glucose metabolism regulates leptin secretion from cultured rat adipocytes. Endocrinology. 1998;139(2):551-558.
• Wellhoener P, Fruehwald-Schultes B, Kern W, Dantz D, Kerner W, Born J, et al. Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans. The Journal of Clinical Endocrinology & Metabolism. 2000;85(3):1267-1271.
• Sonnenberg GE, Krakower GR, Hoffmann RG, Maas DL, Hennes MM, Kissebah AH. Plasma leptin concentrations during extended fasting and graded glucose infusions: relationships with changes in glucose, insulin, and FFA. The Journal of Clinical Endocrinology & Metabolism. 2001;86(10):4895-4900.
• El Dayem SMA, El Kader MA, Ibrahim S, Mokhtar E, El Megeed EA. Leptin and Lipid Profile in Overweight Patient with Type 1 Diabetes. Open access Macedonian journal of medical sciences. 2017;5(2):131.
• Verrotti A, Basciani F, Morgese G, Chiarelli F. Leptin levels in non-obese and obese children and young adults with type 1 diabetes mellitus. European journal of endocrinology. 1998;139(1):49-53.
• Danne T, Grüters A, Wladimirova A, Weber B, Horn R, Mayr B, et al. Gender-specific differences of serum leptin in obese and normal-weight adolescents: studies in type-I diabetes and Turner syndrome. Hormone Research in Paediatrics. 1997;48(3):103-107.
• Luna R, Garcia‐Mayor RV, Lage M, Andrade MA, Barreiro J, Pombo M, et al. High serum leptin levels in children with type 1 diabetes mellitus: contribution of age, BMI, pubertal development and metabolic status. Clinical endocrinology. 1999;51(5):603-610.
• Raisingani M, Preneet B, Kohn B, Yakar S. Skeletal growth and bone mineral acquisition in type 1 diabetic children; abnormalities of the GH/IGF-1 axis. Growth Hormone & IGF Research. 2017;34:13-21.