Article

Influence of AMP-activated protein kinase and calcineurin on metabolic networks in skeletal muscle.

Karolinska Institutet, Dept. of Molecular Medicine and Surgery, von Eulers väg 4, S-171 77 Stockholm, Sweden.
AJP Endocrinology and Metabolism (impact factor: 4.75). 07/2008; 295(3):E545-52. DOI:10.1152/ajpendo.90259.2008 pp.E545-52
Source: PubMed

ABSTRACT Skeletal muscle fibers differ considerably in their metabolic and physiological properties. Skeletal muscle displays a high degree of metabolic flexibility, which allows the myofibers to adapt to various physiological demands by shifting energy substrate utilization. Transcriptional events play a pivotal role in the metabolic adaptations of skeletal muscle. The expression of genes essential for skeletal muscle glucose and lipid metabolism is tightly coordinated in support of a shift in substrate utilization. AMP-activated protein kinase (AMPK) and calcineurin (a calcium-regulated serine/threonine protein phosphatase) regulate skeletal muscle metabolic gene expression programs in response to changes in the energy status and levels of neuronal input, respectively. AMPK and calcineurin activate transcriptional regulators such as peroxisome proliferator-activated receptor-gamma coactivator-1alpha and myocyte enhancer factor as well as increase skeletal muscle oxidative capacity and mitochondrial gene expression. Activation of either the AMPK or calcineurin pathway can also enhance the glycogen storage capacity and insulin sensitivity in skeletal muscle. Characterization of pathways governing skeletal muscle metabolism offers insight into physiological and pharmacological strategies to prevent or ameliorate peripheral insulin resistance associated with metabolic disorders such as type 2 diabetes.

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    Article: Regulation of skeletal muscle sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase (SNARK) by metabolic stress and diabetes.
    A Rune, M E Osler, T Fritz, J R Zierath
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    ABSTRACT: 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 alpha2 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.
    Diabetologia 08/2009; 52(10):2182-9. · 6.81 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

ameliorate peripheral insulin resistance
 
AMP-activated protein kinase
 
calcineurin activate transcriptional regulators
 
calcium-regulated serine/threonine protein phosphatase
 
energy substrate utilization
 
glycogen storage capacity
 
increase skeletal muscle oxidative capacity
 
metabolic adaptations
 
metabolic disorders
 
metabolic flexibility
 
mitochondrial gene expression
 
peroxisome proliferator-activated receptor-gamma coactivator-1alpha
 
physiological properties
 
skeletal muscle
 
Skeletal muscle fibers
 
skeletal muscle glucose
 
skeletal muscle metabolic gene expression programs
 
skeletal muscle metabolism
 
type 2 diabetes
 
various physiological demands
 

Yun Chau Long