کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10755950 | 1050378 | 2014 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Development of in vitro model of insulin receptor cleavage induced by high glucose in HepG2 cells
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کلمات کلیدی
OGTPUGNAcO-linked N-acetylglucosaminePNGase FO-GlcNAcylationOGAO-GlcNAcMMPSIRADAM - آدامBAPTA-AM - بیایپیتیای-AMa disintegrin and metalloprotease - تخریب و متالوپروتئازDON - دونShedding - ریختنHepG2 cells - سلولهای HepG2matrix metalloproteinase - ماتریکس متالوپروتئینازinsulin receptor - گیرنده انسولین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Soluble insulin receptor (sIR), the ectodomain of IR, has been detected in human plasma, and its concentration parallels that of blood glucose in patients with diabetes. IR has a pivotal role in glucose homeostasis and diabetes development; therefore, cleavage of IR promoted by hyperglycemia is involved in insulin resistance and glucose toxicity. To elucidate the physiology of sIR, we developed an in vitro model mimicking the changes in sIR levels in plasma from patients with diabetes. Among four human cell lines that expressed IR, spontaneous cleavage of IR occurred only in HepG2 cells. The molecular characteristics of sIR derived from HepG2 cells were similar to those of sIR detected in human plasma. The concentration of sIR in the medium did not differ between basal and high-glucose conditions in the initial 24-h period, but increasing the duration of pre-stimulation (>48Â h) led to a significant increase in sIR levels in cells exposed to high glucose. Additionally, glucose-dependent increment of sIR was reversible in this model. These results are consistent with the observation of plasma sIR in patients with diabetes. Using this model, O-linked N-acetylglucosamine modification was determined to be involved in high-glucose-induced IR cleavage. A calcium-dependent protease was shown to cleave IR extracellularly. These findings show that this in vitro model could be useful for determining the molecular mechanism underlying IR cleavage.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 445, Issue 1, 28 February 2014, Pages 236-243
Journal: Biochemical and Biophysical Research Communications - Volume 445, Issue 1, 28 February 2014, Pages 236-243
نویسندگان
Tomoyuki Yuasa, Kikuko Amo, Shuhei Ishikura, Hisao Nagaya, Keiji Uchiyama, Seiichi Hashida, Yousuke Ebina,