Insulin gene mutations and diabetes.
Insulin gene mutations and diabetes.
复制标题
DOI：
10.1111/j.2040-1124.2011.00100.x
复制
发表时间：
2011-04-07
影响因子：
3.2
通讯作者：
Nanjo K
中科院分区：
文献类型：
--
作者：
Nishi M;Nanjo K
胰岛素基因的一些突变引起高胰岛素血症或高胰岛素原血症。替代生物上重要的氨基酸会导致受体结合缺陷、半衰期延长和高胰岛素血症。已经确定了三种突变胰岛素：(i)芝加哥胰岛素（F49L或PheB25Leu）；（ii）胰岛素洛杉矶（F48S或PheB24Ser）；（iii）和歌山胰岛素（V92L或ValA3Leu）。氨基酸的替换是胰岛素原加工导致高胰岛素原血症所必需的。已经确定了四种类型：(i) proinsulin Providence (H34D)；（ii）胰岛素原Tokyo (R89H)；（iii）胰岛素原Kyoto (R89L)；（iv）牛津胰岛素原（R89P）。其中三个是处理位点突变。相比之下，原胰岛素的突变被认为会导致分选异常。与正常的胰岛素原相比，大量的胰岛素原进入不发生加工的构成途径。这些胰岛素基因突变与高（前）胰岛素血症非常罕见，仅表现为轻度糖尿病或葡萄糖耐受不良，高（前）胰岛素血症是诊断的关键。然而，在胰岛素基因突变被确定为新生儿糖尿病的原因后，这种情况发生了巨大变化。这类胰岛素基因突变不表现为高（前）胰岛素血症。半胱氨酸残基突变或产生新的半胱氨酸会扰乱正确的二硫键和正确的构象，最终导致胰岛素原折叠错误积聚、内质网应激和胰腺β细胞凋亡。成熟型发病的年轻人糖尿病（MODY）或自身抗体阴性的1型样表型也有报道。最近，胰岛素生物合成减少的隐性突变已被报道。胰岛素基因突变在糖尿病发病机制中的重要性将大大增加，并使我们对β细胞生物学和糖尿病有了新的认识。[J] .糖尿病投资，doi: 10.1111/ J .2040‐1124.2011.00100。x, 2011)
Some mutations of the insulin gene cause hyperinsulinemia or hyperproinsulinemia. Replacement of biologically important amino acid leads to defective receptor binding, longer half‐life and hyperinsulinemia. Three mutant insulins have been identified: (i) insulin Chicago (F49L or PheB25Leu); (ii) insulin Los Angeles (F48S or PheB24Ser); (iii) and insulin Wakayama (V92L or ValA3Leu). Replacement of amino acid is necessary for proinsulin processing results in hyperproinsulinemia. Four types have been identified: (i) proinsulin Providence (H34D); (ii) proinsulin Tokyo (R89H); (iii) proinsulin Kyoto (R89L); and (iv) proinsulin Oxford (R89P). Three of these are processing site mutations. The mutation of proinsulin Providence, in contrast, is thought to cause sorting abnormality. Compared with normal proinsulin, a significant amount of proinsulin Providence enters the constitutive pathway where processing does not occur. These insulin gene mutations with hyper(pro)insulinemia were very rare, showed only mild diabetes or glucose intolerance, and hyper(pro)insulinemia was the key for their diagnosis. However, this situation changed dramatically after the identification of insulin gene mutations as a cause of neonatal diabetes. This class of insulin gene mutations does not show hyper(pro)insulinemia. Mutations at the cysteine residue or creating a new cysteine will disturb the correct disulfide bonding and proper conformation, and finally will lead to misfolded proinsulin accumulation, endoplasmic reticulum stress and apoptosis of pancreatic β‐cells. Maturity‐onset diabetes of the young (MODY) or an autoantibody‐negative type 1‐like phenotype has also been reported. Very recently, recessive mutations with reduced insulin biosynthesis have been reported. The importance of insulin gene mutation in the pathogenesis of diabetes will increase a great deal and give us a new understanding of β‐cell biology and diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00100.x, 2011)
登录
查看更多内容
影响因子：
--
作者：
Boesgaard TW;Pruhova S;Andersson EA;Cinek O;Obermannova B;Lauenborg J;Damm P;Bergholdt R;Pociot F;Pisinger C;Barbetti F;Lebl J;Pedersen O;Hansen T
通讯作者：
Hansen T
人类胰岛素基因的七种突变与永久性新生儿/婴幼儿糖尿病有关
影响因子：
15.9
作者：
Colombo, Carlo;Porzio, Ottavia;Barbetti, Fabrizio
通讯作者：
Barbetti, Fabrizio
影响因子：
4
作者：
Fonseca, Sonya G.;Burcin, Mark;Gromada, Jesper;Urano, Fumihiko
通讯作者：
Urano, Fumihiko
影响因子：
30.5
作者：
Derbinski, J;Schulte, A;Klein, L
通讯作者：
Klein, L
影响因子：
7.7
作者：
Gupta S;McGrath B;Cavener DR
通讯作者：
Cavener DR