An activating mutation of AKT2 and human hypoglycemia.
An activating mutation of AKT2 and human hypoglycemia.
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DOI：
10.1126/science.1210878
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发表时间：
2011-10-28
期刊：
影响因子：
--
通讯作者：
Semple RK
中科院分区：
文献类型：
--
作者：
Hussain K;Challis B;Rocha N;Payne F;Minic M;Thompson A;Daly A;Scott C;Harris J;Smillie BJ;Savage DB;Ramaswami U;De Lonlay P;O'Rahilly S;Barroso I;Semple RK
人类的病理性空腹低血糖通常被解释为循环中的胰岛素或胰岛素样分子过多，或者是先天的代谢错误损害了肝脏葡萄糖的产生。我们研究了三名无血缘关系的儿童，他们患有不明原因的、反复发作的和严重的空腹低血糖和不对称性过度生长。所有的人都在丝氨酸/苏氨酸激酶AKT2中发现了相同的从头突变p.Glu17Lys，其中两例为杂合子，一例为嵌合体。在异源细胞中，突变的AKT2被结构性地招募到质膜上，导致下游信号的胰岛素非依赖性激活。这代表了一种全身性代谢性疾病的新机制，其特征是通常由胰岛素控制的信号通路的结构性、细胞自主激活。
Pathological fasting hypoglycemia in humans is usually explained by excessive circulating insulin or insulin-like molecules, or by inborn errors of metabolism impairing liver glucose production. We studied three unrelated children with unexplained, recurrent and severe fasting hypoglycemia and asymmetrical overgrowth. All were found to carry the same de novo mutation, p.Glu17Lys, in the serine/threonine kinase AKT2, in two cases as heterozygotes and, in one case, in mosaic form. In heterologous cells, the mutant AKT2 was constitutively recruited to the plasma membrane, leading to insulin-independent activation of downstream signaling. This represents a novel mechanism of systemic metabolic disease, characterised by constitutive, cell-autonomous activation of signaling pathways normally controlled by insulin.
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影响因子：
56.9
作者：
Cho, H;Mu, J;Birnbaum, MJ
通讯作者：
Birnbaum, MJ
影响因子：
--
作者：
Hussain, K;Bodamer, O A F;Aynsley-Green, A
通讯作者：
Aynsley-Green, A
DOI：
10.1056/nejmoa1104017
发表时间：
2011-08-18
期刊：
The New England journal of medicine
影响因子：
--
作者：
Lindhurst MJ;Sapp JC;Teer JK;Johnston JJ;Finn EM;Peters K;Turner J;Cannons JL;Bick D;Blakemore L;Blumhorst C;Brockmann K;Calder P;Cherman N;Deardorff MA;Everman DB;Golas G;Greenstein RM;Kato BM;Keppler-Noreuil KM;Kuznetsov SA;Miyamoto RT;Newman K;Ng D;O'Brien K;Rothenberg S;Schwartzentruber DJ;Singhal V;Tirabosco R;Upton J;Wientroub S;Zackai EH;Hoag K;Whitewood-Neal T;Robey PG;Schwartzberg PL;Darling TN;Tosi LL;Mullikin JC;Biesecker LG
通讯作者：
Biesecker LG
影响因子：
64.8
作者：
Carpten, John D.;Faber, Andrew L.;Thomas, James E.
通讯作者：
Thomas, James E.
影响因子：
56.9
作者：
George, S;Rochford, JJ;Wolfrum, C;Gray, SL;Schinner, S;Wilson, JC;Soos, MA;Murgatroyd, PR;Williams, RM;Acerini, CL;Dunger, DB;Barford, D;Umpleby, AM;Wareham, NJ;Davies, HA;Schafer, AJ;Stoffel, M;O'Rahilly, S;Barroso, I
通讯作者：
Barroso, I