Regulation of skeletal muscle sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase (SNARK) by metabolic stress and diabetes.
Regulation of skeletal muscle sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase (SNARK) by metabolic stress and diabetes.
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DOI：
10.1007/s00125-009-1465-x
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发表时间：
2009-10
期刊：
影响因子：
8.2
通讯作者：
Zierath, J. R.
中科院分区：
文献类型：
--
作者：
Rune, A.;Osler, M. E.;Fritz, T.;Zierath, J. R.
关键词：
蔗糖，非发酵1/ amp活化蛋白激酶相关激酶（SNARK）参与与肥胖和2型糖尿病相关的细胞应激反应。我们确定了SNARK在代谢应激和胰岛素对骨骼肌葡萄糖和脂质代谢的作用中的作用。从正常葡萄糖耐受性（n = 35）和2型糖尿病（n = 31）的男性和女性中获得股外侧骨骼肌活检，用于SNARK表达研究。原代肌管培养来源于正常葡萄糖耐受性个体的活组织检查，用于代谢研究。SNARK（也称为NUAK2） mRNA表达在正常糖耐量个体和2型糖尿病患者之间没有改变。SNARK在肥胖（BMI < 31 kg/m2）正常糖耐量个体和2型糖尿病患者骨骼肌中的表达比超重（BMI <28 kg/m2）正常糖耐量个体和2型糖尿病患者的骨骼肌表达增加（分别为1.4和1.4倍，p < 0.05）。暴露于棕榈酸盐（12倍，p < 0.01）或TNF-α（25倍，p < 0.05）的肌管中SNARK mRNA增加，但油酸盐、葡萄糖或IL-6没有增加，而amp活化的蛋白激酶α2亚基的表达不变。SNARK的小干扰RNA （si）分别使肌管mRNA和蛋白减少61%和60% （p < 0.05）。SNARK siRNA对基础或胰岛素刺激的葡萄糖摄取或脂质氧化没有影响，不足以挽救TNF-α-或棕榈酸盐诱导的胰岛素抵抗。骨骼肌SNARK表达在人类肥胖和代谢应激源中增加，但在2型糖尿病中没有。部分SNARK消耗不能改变葡萄糖或脂质代谢，也不能防止TNF-α-或棕榈酸盐诱导的原发性人肌管胰岛素抵抗。
Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase (SNARK) is involved in cellular stress responses linked to obesity and type 2 diabetes. We determined the role of SNARK in response to metabolic stress and insulin action on glucose and lipid metabolism in skeletal muscle. Vastus lateralis skeletal muscle biopsies were obtained from normal glucose tolerant (n = 35) and type 2 diabetic (n = 31) men and women for SNARK expression studies. Primary myotube cultures were derived from biopsies obtained from normal glucose tolerant individuals for metabolic studies. SNARK (also known as NUAK2) mRNA expression was unaltered between normal glucose tolerant individuals and type 2 diabetic patients. SNARK expression was increased in skeletal muscle from obese (BMI >31 kg/m2) normal glucose tolerant individuals and type 2 diabetic patients (1.4- and 1.4-fold, respectively, p < 0.05) vs overweight (BMI <28 kg/m2) normal glucose tolerant individuals and type 2 diabetic patients. SNARK mRNA was increased in myotubes exposed to palmitate (12-fold; p < 0.01), or TNF-α (25-fold, p < 0.05), but not to oleate, glucose or IL-6, whereas expression of the AMP-activated protein kinase α2 subunit was unaltered. Small interfering (si)RNA against SNARK reduced mRNA and protein in myotubes by 61% and 60%, respectively (p < 0.05). SNARK siRNA was without effect on basal or insulin-stimulated glucose uptake or lipid oxidation, and insufficient to rescue TNF-α- or palmitate-induced insulin resistance. Skeletal muscle SNARK expression is increased in human obesity, and in response to metabolic stressors, but not type 2 diabetes. Partial SNARK depletion failed to modify either glucose or lipid metabolism, or protect against TNF-α- or palmitate-induced insulin resistance in primary human myotubes.
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DOI：
10.1152/ajpendo.90891.2008
发表时间：
2009-05-01
影响因子：
5.1
作者：
Ichinoseki-Sekine, Noriko;Naito, Hisashi;Esumi, Hiroyasu
通讯作者：
Esumi, Hiroyasu
影响因子：
4
作者：
Al-Hakim, AK;Göransson, O;Alessi, DR
通讯作者：
Alessi, DR
DOI：
10.1152/ajpendo.00178.2009
发表时间：
2009-05-01
影响因子：
5.1
作者：
Egan, Brendan;Zierath, Juleen R.
通讯作者：
Zierath, Juleen R.
DOI：
10.1016/j.bbrc.2008.10.143
发表时间：
2008-12-26
影响因子：
3.1
作者：
Kuga, Wataru;Tsuchihara, Katsuya;Esumi, Hiroyasu
通讯作者：
Esumi, Hiroyasu
DOI：
10.1152/ajpcell.1995.268.4.c846
发表时间：
1995-04-01
影响因子：
5.5
作者：
ROSEN, CF;POON, R;DRUCKER, DJ
通讯作者：
DRUCKER, DJ