大鼠BTCe对体外培养胰岛保护作用及对糖尿病大鼠降糖作用的研究
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国家自然科学基金资助项目(30470817),上海市科委课题(04DZ19507)


Study of The Effect on Islets Cultured In vitro and STZ-induced Diabetic Rats In vivo of EGF-like Domain of Betacellulin
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This work was supported by grants from The National Natural Science Foundation of China (30470817), The Key Program of Shanghai (04DZ19507), The Talent Youth Culture Plan of Tongji University and The Venus Fund of Shanghai the Tenth People's Hospital.

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    摘要:

    β细胞素 (betacellulin,BTC) 是目前较受关注的胰岛再生因子,但其促胰腺、胰岛再生的机制不清. BTCe是betacellulin的功能片段,促细胞增殖能力与BTC相同. 实验通过原核表达方法获得BTCe蛋白,MTT法证实其促3T3-L1细胞增殖能力. 将BTC或BTCe作用于原代培养的大鼠胰岛,观察其对胰岛分泌的急性及长期影响作用,实时定量PCR及免疫荧光检测胰岛内关键基因的表达. 将质粒pcDNA3.1-BTCe注射入链脲霉素 (STZ) 诱导的糖尿病大鼠肌肉中,观察对大鼠血糖的影响作用. 加入BTC或BTCe可明显提高体外培养大鼠胰岛的GSIS水平,但实时定量PCR及免疫荧光显示胰岛内4种关键基因的表达并无明显变化;pcDNA3.1-BTCe转染糖尿病大鼠15~20天后血糖出现下降,糖耐量明显改善;免疫荧光显示:胰腺内有大量PDX-1的导管细胞及胰岛素阳性细胞出现. 推测BTC及BTCe对体外长期培养的大鼠胰岛具有一定的保护作用,可能通过促进胰腺内PDX-1的导管细胞及胰岛素阳性细胞的增殖、诱导对STZ诱导的糖尿病大鼠的高血糖具有一定缓解作用.

    Abstract:

    Betacellulin (BTC) is one of “islets regeneration factors” which received more and more attention these years. BTCe is the C-terminal 50-residue region of mature BTC protein and can bind with erbB-1、erbB-4 receptor. It has the same mitogenic activity on cells as the whole section. BTC and BTCe can improve the level of glucose-stimulated insulin secretion (GSIS) during islets culture in vitro though they had no effect on the acute insulin secretion. BTCe also effectively ameliorated the hyperglycemia of STZ-induced diabetic rats by a single plasmid injection into muscle of rats. It is supposed that BTCe promote the proliferation of PDX-1 positive cells or repair some signal transduction pathway. Perhaps the latter is more important.

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李鸿,周伟斌,李凤英,顾燕云,田璟琰,钱 镭,张 迪,周文中,吴国亭,骆天红,李 果,罗 敏.大鼠BTCe对体外培养胰岛保护作用及对糖尿病大鼠降糖作用的研究[J].生物化学与生物物理进展,2006,33(12):1190-1199

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  • 收稿日期:2006-05-12
  • 最后修改日期:2006-09-20
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  • 在线发布日期: 2006-12-15
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