Abstract
Amac: Diabetes mellitus ikincil komplikasyon olarak noropatiye neden olmaktadir. Diyabetik noropatinin temel mekanizmasi beyindeki glukoz homeostasisinin ve enerji dengesinin bozulmasidir. Bu calismanin amaci anti-diyabetik bilesik olarak kurkuminin diyabetik sican beyinlerinde IRS1, Grb2, K-Ras ve Bax proteinlerinin ekspresyonlari uzerindeki etkisinin belirlenmesidir. Materyal-Metot: 16 adet Wistar albino sican rastgele 4’ erli gruplar halinde 4 gruba ayrilmistir; kontrol grup, kurkumin grup, STZ muamele grup ve STZ+kurkumin muamele grup. STZ gruplarindaki sicanlarda diyabet, intraperitonel STZ uygulamasi ile induklenmistir. Ardindan hayvanlar, gunluk gavaj uygulamasiyla kurkumin ile muamele edilmistir. IRS1, Grb2, K-Ras ve Bax ekspresyon ve aktivasyonu western blot yontemi ile belirlenmistir. Sonuclar: Western blot analizleri, kurkumin muamelesinin IRS1 aktivasyonunu arttirdigini ve STZ’nin IRS1 aktivasyonu uzerindeki negatif etkisini geriye cevirdigini gostermektedir. STZ grubunda K-Ras ekspresyonu belirgin bir derecede azalirken, Bax ekspresyonu artmistir (p<0.05). Tum gruplarda, Grb2 ve IRS1 ekpresyonlarinda herhangi bir degisiklik gozlemlenmemistir. Sonuc: Sonuclar goz onune alindiginda, STZ induklu diyabetik sican beyinlerinde kurkumin muamelesinin STZ’nin insulin sinyali yolagi elemanlari uzerindeki negatif etkilerini geriye cevirdigi soylenebilmektedir.
Highlights
Diabetes mellitus is a multifactorial complex metabolic disease group characterized by hyperglycemia resulting from the defects in insulin signaling
Curcumin treatment led to an increase in the phosphorylation of IRS1 in curcumin+STZ group compared to STZ group (p=0.003)
Significant change was not observed in tyrosinephosphorylation level of IRS1 in STZ+Curcumin group compared to Curcumin group (Figure 1a)
Summary
Diabetes mellitus is a multifactorial complex metabolic disease group characterized by hyperglycemia resulting from the defects in insulin signaling. Dysregulation in glucose homeostasis and energy balance induces the pathological processes such as oxidative stress and abnormal inflammatory response that lead to neuronal loss or death in diabetes mellitus [2]. Insulin is the primary anabolic hormone that controls energy balance and glucose homeostasis through complex cellular signaling pathways in body. Insulin receptor substrate (IRS) proteins are the main docking proteins that bind insulin and insulin like growth factor receptors and transmit the signal to the downstream targets such as Growth factor receptorbound protein 2 (Grb2), Rat sarcoma viral oncogene homolog (RAS), Extracellular signal-regulated kinases (ERK1/2), Phosphoinositide 3-kinase (PI3K) and Protein kinase B (AKT) [3]. Tyrosine phosphorylations of IRS1 protein trigger the insulin signaling, serine/threonine (S/T) phosphorylations generally inhibit the signal transduction.
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