Regulation of skeletal muscle sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase (SNARK) by metabolic stress and diabetes

被引：30

作者：

Rune, A. ^{[1
]}

Osler, M. E. ^{[1
]}

Fritz, T. ^{[2
]}

Zierath, J. R. ^{[1
]}

机构：

[1] Karolinska Inst, Dept Mol Med & Surg, Sect Integrat Physiol, S-17177 Stockholm, Sweden

[2] Karolinska Inst, Ctr Family Med, Huddinge, Sweden

来源：

DIABETOLOGIA | 2009年 / 52卷 / 10期

基金：

瑞典研究理事会; 欧洲研究理事会;

关键词：

AMPK activation; Glucose metabolism; Insulin resistance; Lipid metabolism; Obesity; Palmitate; Signal transduction; siRNA; TNF-alpha; Type; 2; diabetes; TUMOR-NECROSIS-FACTOR; GLUCOSE-UPTAKE; LKB1; AMPK; CONTRACTION; CELL; DIFFERENTIATION; IDENTIFICATION; LOCALIZATION; KNOCKOUT;

D O I：

10.1007/s00125-009-1465-x

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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/m(2)) normal glucose tolerant individuals and type 2 diabetic patients (1.4- and 1.4-fold, respectively, p < 0.05) vs overweight (BMI < 28 kg/m(2)) 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-alpha (25-fold, p < 0.05), but not to oleate, glucose or IL-6, whereas expression of the AMP-activated protein kinase alpha 2 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-alpha- 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-alpha- or palmitate-induced insulin resistance in primary human myotubes.

引用

页码：2182 / 2189

页数：8

共 25 条

[1] 14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and SIK [J].

Al-Hakim, AK ;

Göransson, O ;

Deak, M ;

Toth, R ;

Campbell, DG ;

Morrice, NA ;

Prescott, AR ;

Alessi, DR .

JOURNAL OF CELL SCIENCE, 2005, 118 (23) :5661-5673

[2] Human skeletal muscle cell differentiation is associated with changes in myogenic markers and enhanced insulin-mediated MAPK and PKB phosphorylation [J].

Al-Khalili, L ;

Krämer, D ;

Wretenberg, P ;

Krook, A .

ACTA PHYSIOLOGICA SCANDINAVICA, 2004, 180 (04) :395-403

[3] Insulin action in cultured human skeletal muscle cells during differentiation: assessment of cell surface GLUT4 and GLUT1 content [J].

Al-Khalili, L ;

Chibalin, AV ;

Kannisto, K ;

Zhang, BB ;

Permert, J ;

Holman, GD ;

Ehrenborg, E ;

Ding, VDH ;

Zierath, JR ;

Krook, A .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2003, 60 (05) :991-998

[4] Signaling specificity of interleukin-6 action on glucose and lipid metabolism in skeletal muscle [J].

Al-Khalili, Lubna ;

Bouzakri, Karim ;

Glund, Stephan ;

Lonnqvist, Fredrik ;

Koistinen, Heikki A. ;

Krook, Anna .

MOLECULAR ENDOCRINOLOGY, 2006, 20 (12) :3364-3375

[5] SiRNA-mediated reduction of inhibitor of nuclear factor-κB kinase prevents tumor necrosis factor-α-induced insulin resistance in human skeletal muscle [J].

Austin, Reginald L. ;

Rune, Anna ;

Bouzakri, Karim ;

Zierath, Juleen R. ;

Krook, Anna .

DIABETES, 2008, 57 (08) :2066-2073

[6] MAP4K4 gene silencing in human skeletal muscle prevents tumor necrosis factor-α-induced insulin resistance [J].

Bouzakri, Karim ;

Zierath, Juleen R. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (11) :7783-7789

[7] Hunting for the SNARK in metabolic disease [J].

Egan, Brendan ;

Zierath, Juleen R. .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2009, 296 (05) :E969-E972

[8] AMPK: a key regulator of energy balance in the single cell and the whole organism [J].

Hardie, D. G. .

INTERNATIONAL JOURNAL OF OBESITY, 2008, 32 (Suppl 4) :S7-S12

[9] Provision of a voluntary exercise environment enhances running activity and prevents obesity in Snark-deficient mice [J].

Ichinoseki-Sekine, Noriko ;

Naito, Hisashi ;

Tsuchihara, Katsuya ;

Kobayashi, Ikumi ;

Ogura, Yuji ;

Kakigi, Ryo ;

Kurosaka, Mitsutoshi ;

Fujioka, Rumi ;

Esumi, Hiroyasu .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2009, 296 (05) :E1013-E1021

[10] Knockout of the α2 but not α1 5′-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside- but not contraction-induced glucose uptake in skeletal muscle [J].

Jorgensen, SB ;

Viollet, B ;

Andreelli, F ;

Frosig, C ;

Birk, JB ;

Schjerling, P ;

Vaulont, S ;

Richter, EA ;

Wojtaszewski, JFP .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (02) :1070-1079

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