کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10738472 | 1046708 | 2011 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Tat-enhanced delivery of metallothionein can partially prevent the development of diabetes
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کلمات کلیدی
transactivator of transcriptionNF-κBATF6eIF2αXBP1GFPIRE1T2DHOMA-IRSTZ3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide - 3- (4،5-dimethylthiazol-2-yl) -2،5-difenyltetrazolium bromideHOMA-β - HOMA-bMTT - MTTROS - ROSER stress - استرس استstreptozotocin - استرپتوزوتوسینTAT - تاتInsulin secretion - ترشح انسولینOxidative stress - تنش اکسیداتیوCHOP - تکه کردنDiabetes mellitus - دیابت قندیType 2 diabetes mellitus - دیابت نوع دوFree radicals - رادیکال آزادeukaryotic initiation factor 2α - عامل آغاز کننده یوکاریوتی 2αactivating transcription factor 6 - فعال کردن عامل رونویسی 6Metallothionein - متالوتونیئینInsulin resistance - مقاومت به انسولینHIV-1 - ویروس اچ آی وی نوع یکHuman immunodeficiency virus type 1 - ویروس نقص ایمنی بدن نوع 1X-box-binding protein 1 - پروتئین X-box binding 1green fluorescent protein - پروتئین فلورسنت سبزCCAAT/enhancer-binding protein homologous protein - پروتئین هموسیستون پروتئین پروتئین CCAAT / پروتئین تقویت کنندهReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Metallothioneins (MTs) are intracellular low-molecular-weight, cysteine-rich proteins with potent metal-binding and redox functions, but with limited membrane permeativity. The aim of this study was to investigate whether we could enhance delivery of MT-1 to pancreatic islets or β cells in vitro and in vivo. The second goal was to determine whether increased MT-1 could prevent cellular toxicity induced by high glucose and free fatty acids in vitro (glucolipotoxicity) and ameliorate the development of diabetes induced by streptozotocin in mice or delay the development of diabetes by improving insulin secretion and resistance in the OLETF rat model of type 2 diabetes. Expression of HIV-1 Tat-MT-1 enabled efficient delivery of MT into both INS-1 cells and rat islets. Intracellular MT activity increased in parallel with the amount of protein delivered to cells. The formation of reactive oxygen species, glucolipotoxicity, and DNA fragmentation due to streptozotocin decreased after treating pancreatic β cells with Tat-MT in vitro. Importantly, in vivo, intraperitoneal injection resulted in delivery of the Tat-MT protein to the pancreas as well as liver, muscle, and white adipose tissues. Multiple injections increased radical-scavenging activity, decreased apoptosis, and reduced endoplasmic reticulum stress in the pancreas. Treatment with Tat-MT fusion protein delayed the development of diabetes in streptozotocin-induced mice and improved insulin secretion and resistance in OLETF rats. These results suggest that in vivo transduction of Tat-MT may offer a new strategy to protect pancreatic β cells from glucolipotoxicity, may improve insulin resistance in type 2 diabetes, and may have a protective effect in preventing islet destruction in type 1 diabetes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 51, Issue 9, 1 November 2011, Pages 1666-1674
Journal: Free Radical Biology and Medicine - Volume 51, Issue 9, 1 November 2011, Pages 1666-1674
نویسندگان
Leejin Park, Dongsoo Min, Hyunok Kim, Hee-Yong Chung, Chul-Hoon Lee, In-Sun Park, Yonghee Kim, Yongsoo Park,