| ? | ||||||||||||
|
||||||||||||
 |
 |
 |
 |
 |
 |
 |
 |
 |
 |
| 購買進(jìn)口儀器、試劑和耗材——就在始于2001年的畢特博生物 m.pyjb.com.cn |
日本研究人員在新一期美國《臨床研究期刊》（The Journal of Clinical Investigation）網(wǎng)絡(luò)版上發(fā)表論文指出，很多并不肥胖的日本人也會患Ⅱ型糖尿病，這是他們體內(nèi)的特定基因出現(xiàn)變異，導(dǎo)致有降血糖功效的胰島素分泌減少引起的。 Ⅱ型糖尿病又稱成年發(fā)病型糖尿病，是最常見的糖尿病，其特點是胰島素抵抗，即體內(nèi)組織對胰島素的作用不敏感，正常量的胰島素起不到正常的降血糖作用，或胰島素分泌不足。包括日本人在內(nèi)的亞洲人種的Ⅱ型糖尿病患者往往并不伴有肥胖等特征。不肥胖者也會患糖尿病的原因迄今不明。 日本熊本大學(xué)研究生院教授富澤一仁率領(lǐng)的研究小組在利用實驗鼠進(jìn)行的研究中發(fā)現(xiàn)，多種氨基酸在胰腺中組合，生成胰島素的時候，一種名為“CDKAL1”的基因能促進(jìn)氨基酸正確組合。這種基因若因變異而不能發(fā)揮作用，異常的胰島素就會增加，進(jìn)而妨礙正常胰島素的分泌。在這種基因變異的情況下，即使實驗鼠并不肥胖，也會患上Ⅱ型糖尿病。 據(jù)調(diào)查，在亞洲，每4個人中就有1人的“CDKAL1”基因出現(xiàn)變異，而只有10%左右的歐美人體內(nèi)這種基因會出現(xiàn)變異。富澤一仁指出：“現(xiàn)在，不管什么人種都使用相同的糖尿病治療藥物，此次發(fā)現(xiàn)將有利于開發(fā)對亞洲人種更加有效的藥物。”
doi:10.1172/JCI58056. Deficit of tRNALys modification by Cdkal1 causes the development of type 2 diabetes in mice Fan-Yan Wei, Takeo Suzuki, Sayaka Watanabe, Satoshi Kimura, Taku Kaitsuka, Atsushi Fujimura, Hideki Matsui, Mohamed Atta, Hiroyuki Michiue, Marc Fontecave, Kazuya Yamagata, Tsutomu Suzuki and Kazuhito Tomizawa The worldwide prevalence of type 2 diabetes (T2D), which is caused by a combination of environmental and genetic factors, is increasing. With regard to genetic factors, variations in the gene encoding Cdk5 regulatory associated protein 1–like 1 (Cdkal1) have been associated with an impaired insulin response and increased risk of T2D across different ethnic populations, but the molecular function of this protein has not been characterized. Here, we show that Cdkal1 is a mammalian methylthiotransferase that biosynthesizes 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A) in tRNALys(UUU) and that it is required for the accurate translation of AAA and AAG codons. Mice with pancreatic β cell–specific KO of Cdkal1 (referred to herein as β cell KO mice) showed pancreatic islet hypertrophy, a decrease in insulin secretion, and impaired blood glucose control. In Cdkal1-deficient β cells, misreading of Lys codon in proinsulin occurred, resulting in a reduction of glucose-stimulated proinsulin synthesis. Moreover, expression of ER stress–related genes was upregulated in these cells, and abnormally structured ER was observed. Further, the β cell KO mice were hypersensitive to high fat diet–induced ER stress. These findings suggest that glucose-stimulated translation of proinsulin may require fully modified tRNALys(UUU), which could potentially explain the molecular pathogenesis of T2D in patients carrying cdkal1 risk alleles. |
購買進(jìn)口儀器、試劑和耗材——就在始于2001年的畢特博生物
m.pyjb.com.cn |
|
