Pten (phosphatase and tensin homologue gene) haploinsufficiency promotes insulin hypersensitivity.
Pten (phosphatase and tensin homologue gene) haploinsufficiency promotes insulin hypersensitivity.
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DOI：
10.1007/s00125-006-0531-x
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发表时间：
2007-02
期刊：
影响因子：
8.2
通讯作者：
Ong, C. J.
中科院分区：
文献类型：
--
作者：
Wong, J. T.;Kim, P. T. W.;Peacock, J. W.;Yau, T. Y.;Mui, A. L. -F.;Chung, S. W.;Sossi, V.;Doudet, D.;Green, D.;Ruth, T. J.;Parsons, R.;Verchere, C. B.;Ong, C. J.
胰岛素通过多种信号传导途径控制葡萄糖代谢，包括肌肉和脂肪组织中的磷脂酰肌醇3-激酶（PI 3 K）途径。蛋白质/脂质磷酸酶Pten（10号染色体上缺失的磷酸酶和张力蛋白同源物）通过使PI 3 K产生的磷脂酰肌醇3，4，5-三磷酸去磷酸化来减弱PI 3 K信号传导。本研究旨在研究Pten单倍不足对胰岛素刺激的葡萄糖摄取的影响。在腹腔注射胰岛素激发和葡萄糖耐量试验中研究了Pten杂合（Pten+/-）小鼠的胰岛素敏感性。葡萄糖摄取在Pten+/−小鼠肌细胞原代培养物中进行体外监测，并通过正电子发射断层扫描进行体内监测。蛋白质激酶B（PKB/Akt）（PI 3 K途径的下游信号蛋白）和糖原合成酶激酶3β（GSK 3 β）（PKB/Akt的底物）的磷酸化状态通过蛋白质免疫印迹法测定。腹膜内胰岛素激发后，Pten+/−小鼠的血糖水平持续降低长达120分钟，而野生型小鼠的血糖水平在约30分钟后开始恢复。在葡萄糖激发后，Pten+/−小鼠的血糖恢复正常的速度约为对照组的两倍。通过PET在Pten+/−小鼠的Pten+/−肌细胞和骨骼肌中观察到葡萄糖摄取增强。在Pten+/−心肌细胞中，PKB和GSK 3 β磷酸化增强并延长。Pten是体内外胰岛素刺激葡萄糖摄取的关键负调节因子。由于Pten单倍不足而导致Pten的部分减少足以引起Pten+/-小鼠的胰岛素敏感性和葡萄糖耐量增强。
Insulin controls glucose metabolism via multiple signalling pathways, including the phosphatidylinositol 3-kinase (PI3K) pathway in muscle and adipose tissue. The protein/lipid phosphatase Pten (phosphatase and tensin homologue deleted on chromosome 10) attenuates PI3K signalling by dephosphorylating the phosphatidylinositol 3,4,5-trisphosphate generated by PI3K. The current study was aimed at investigating the effect of haploinsufficiency for Pten on insulin-stimulated glucose uptake. Insulin sensitivity in Pten heterozygous (Pten+/−) mice was investigated in i.p. insulin challenge and glucose tolerance tests. Glucose uptake was monitored in vitro in primary cultures of myocytes from Pten+/− mice, and in vivo by positron emission tomography. The phosphorylation status of protein kinase B (PKB/Akt), a downstream signalling protein in the PI3K pathway, and glycogen synthase kinase 3β (GSK3β), a substrate of PKB/Akt, was determined by western immunoblotting. Following i.p. insulin challenge, blood glucose levels in Pten+/− mice remained depressed for up to 120 min, whereas glucose levels in wild-type mice began to recover after approximately 30 min. After glucose challenge, blood glucose returned to normal about twice as rapidly in Pten+/− mice. Enhanced glucose uptake was observed both in Pten+/− myocytes and in skeletal muscle of Pten+/− mice by PET. PKB and GSK3β phosphorylation was enhanced and prolonged in Pten+/− myocytes. Pten is a key negative regulator of insulin-stimulated glucose uptake in vitro and in vivo. The partial reduction of Pten due to Pten haploinsufficiency is enough to elicit enhanced insulin sensitivity and glucose tolerance in Pten+/− mice.
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DOI：
10.1073/pnas.201167798
发表时间：
2001-09-25
影响因子：
11.1
作者：
Kwabi-Addo, B;Giri, D;Ittmann, M
通讯作者：
Ittmann, M
DOI：
10.1073/pnas.171060098
发表时间：
2001-08-28
影响因子：
11.1
作者：
Podsypanina, K;Lee, RT;Parsons, R
通讯作者：
Parsons, R
影响因子：
--
作者：
Bandyopadhyay, G;Standaert, ML;Farese, RV
通讯作者：
Farese, RV
影响因子：
56.9
作者：
Di Cristofano, A;Kotsi, P;Pandolfi, PP
通讯作者：
Pandolfi, PP
影响因子：
--
作者：
Bandyopadhyay, G;Standaert, ML;Farese, RV
通讯作者：
Farese, RV