日本研究人员在新一期美国《临床检查杂志》网络版上发表论文指出，很多并不肥胖的日本人也会患Ⅱ型糖尿病，这是他们体内的特定基因出现变异，导致有降血糖功效的胰岛素分泌减少引起的。

Ⅱ型糖尿病又称成年发病型糖尿病，是最常见的糖尿病，其特点是胰岛素抵抗，即体内组织对胰岛素的作用不敏感，正常量的胰岛素起不到正常的降血糖作用，或胰岛素分泌不足。包括日本人在内的亚洲人种的Ⅱ型糖尿病患者往往并不伴有肥胖等特征。不肥胖者也会患糖尿病的原因迄今不明。

日本熊本大学研究生院教授富泽一仁率领的研究小组在利用实验鼠进行的研究中发现，多种氨基酸在胰腺中组合，生成胰岛素的时候，一种名为“ＣＤＫＡＬ１”的基因能促进氨基酸正确组合。这种基因若因变异而不能发挥作用，异常的胰岛素就会增加，进而妨碍正常胰岛素的分泌。在这种基因变异的情况下，即使实验鼠并不肥胖，也会患上Ⅱ型糖尿病。

据调查，在亚洲，每４个人中就有１人的“ＣＤＫＡＬ１”基因出现变异，而只有１０％左右的欧美人体内这种基因会出现变异。富泽一仁指出：“现在，不管什么人种都使用相同的糖尿病治疗药物，此次发现将有利于开发对亚洲人种更加有效的药物。”

英文论文摘要：

Deficit of tRNA^Lys modification by Cdkal1 causes the development of type 2 diabetes in mice

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 tRNA^Lys(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 tRNA^Lys(UUU), which could potentially explain the molecular pathogenesis of T2D in patients carrying cdkal1 risk alleles.