Katagiri H, Asano T, Ishihara H, Inukai K, Anai M, Miyazaki J, Tsukuda K, Kikuchi M, Yazaki Y, Oka Y
Third Department of Internal Medicine, University of Tokyo, Japan.
Lancet. 1992 Nov 28;340(8831):1316-7. doi: 10.1016/0140-6736(92)92494-z.
A nonsense mutation at codon 186 in exon 5 of the gene for glucokinase, an enzyme important for glucose-induced insulin secretion, was identified in a Japanese patient with late-onset non-insulin-dependent diabetes mellitus (NIDDM). All affected members of her family were heterozygous for the mutation and had late-onset NIDDM or impaired glucose tolerance, whereas unaffected members showed normal glucose tolerance. The early insulin response to oral glucose was impaired in affected relatives, but was normal in those unaffected. These findings suggest that the glucokinase mutation raises the set-point of pancreatic beta cells for glucose-induced insulin secretion, leading to abnormal glucose tolerance in some patients with late-onset NIDDM.
在一名患有晚发性非胰岛素依赖型糖尿病（NIDDM）的日本患者中，发现葡萄糖激酶（一种对葡萄糖诱导的胰岛素分泌很重要的酶）基因第5外显子第186密码子处存在无义突变。她家族中所有受影响的成员均为该突变的杂合子，患有晚发性NIDDM或糖耐量受损，而未受影响的成员糖耐量正常。受影响亲属对口服葡萄糖的早期胰岛素反应受损，但未受影响的亲属反应正常。这些发现表明，葡萄糖激酶突变提高了胰腺β细胞对葡萄糖诱导的胰岛素分泌的阈值，导致一些晚发性NIDDM患者出现异常糖耐量。
