General Information:

Id: 503
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mus musculus
article
Reference: Dzamko N et al.(2008) AMPK-independent pathways regulate skeletal muscle fatty acid oxidation J. Physiol. (Lond.) 586: 5819-5831 [PMID: 18845612]

Interaction Information:

Comment Defects in skeletal muscle fatty acid oxidation contribute to the pathogenesis of insulin resistance and obesity.
Formal Description
Interaction-ID: 2473

affects_activity of

disease

Insulin resistance

in skeletal muscle
Comment Both AICAR and muscle contractions increased AMPK alpha2 activity in glycolytic (extensor digitorum longus, EDL) and oxidative (soleus, SOL) muscles from wild-type mice.
Formal Description
Interaction-ID: 2476

drug/chemical compound

AICAR

increases_activity of

gene/protein

PRKAA2

in skeletal muscle (EDL and SOL); in wild-type mice
Drugbank entries Show/Hide entries for AICAR
Comment AMPK alpha1 activity was only increased with contraction in extensor digitorum longus (EDL) muscle from wild-type animals.
Formal Description
Interaction-ID: 2477

increases_activity of

gene/protein

PRKAA1

in skeletal muscle (EDL); in wild-type mice
Drugbank entries Show/Hide entries for PRKAA1
Comment AMPK alpha1 activity was only increased with contraction in extensor digitorum longus (EDL) muscle from wild-type animals.
Formal Description
Interaction-ID: 2478

drug/chemical compound

AICAR

NOT increases_activity of

gene/protein

PRKAA1

in skeletal muscle (EDL and SOL); in wild-type mice
Drugbank entries Show/Hide entries for AICAR or PRKAA1
Comment AMPK alpha1 activity was only increased with contraction in extensor digitorum longus (EDL) muscle from wild-type animals.
Formal Description
Interaction-ID: 2479

NOT increases_activity of

gene/protein

PRKAA1

in skeletal muscle (SOL); in wild-type mice
Drugbank entries Show/Hide entries for PRKAA1
Comment Both AICAR and muscle contractions increased AMPK alpha2 activity in glycolytic (extensor digitorum longus, EDL) and oxidative (soleus, SOL) muscles from wild-type mice.
Formal Description
Interaction-ID: 2480

increases_activity of

gene/protein

PRKAA2

in skeletal muscle (EDL and SOL); in wild-type mice
Comment Neither AMPK alpha1 or alpha2 activities were increased in AMPK KD mice (transgenic muscle-specific AMPK alpha2 kinase dead mice) by AICAR or muscle contraction in either muscle type (soleus SOL and extensor digitorum longus EDL).
Formal Description
Interaction-ID: 2481

drug/chemical compound

AICAR

NOT increases_activity of

gene/protein

PRKAA1

in skeletal muscle (EDL and SOL); in AMPK KD mice
Drugbank entries Show/Hide entries for AICAR or PRKAA1
Comment Neither AMPK alpha1 or alpha2 activities were increased in AMPK KD mice (transgenic muscle-specific AMPK alpha2 kinase dead mice) by AICAR or muscle contraction in either muscle type (soleus SOL and extensor digitorum longus EDL).
Formal Description
Interaction-ID: 2482

drug/chemical compound

AICAR

NOT increases_activity of

gene/protein

PRKAA2

in skeletal muscle (EDL and SOL); in AMPK KD mice
Drugbank entries Show/Hide entries for AICAR
Comment Neither AMPK alpha1 or alpha2 activities were increased in AMPK KD mice (transgenic muscle-specific AMPK alpha2 kinase dead mice) by AICAR or muscle contraction in either muscle type (soleus SOL and extensor digitorum longus EDL).
Formal Description
Interaction-ID: 2483

NOT increases_activity of

gene/protein

PRKAA1

in skeletal muscle (EDL and SOL); in AMPK KD mice
Drugbank entries Show/Hide entries for PRKAA1
Comment Neither AMPK alpha1 or alpha2 activities were increased in AMPK KD mice (transgenic muscle-specific AMPK alpha2 kinase dead mice) by AICAR or muscle contraction in either muscle type (soleus SOL and extensor digitorum longus EDL).
Formal Description
Interaction-ID: 2484

NOT increases_activity of

gene/protein

PRKAA2

in skeletal muscle (EDL and SOL); in AMPK KD mice
Comment Both AICAR and muscle contraction increased the phosphorylation of ACC2 to a similar degree in muscle from wild-type and AMPK-KD littermates, although the absolute degree of phosphorylation was modestly reduced in AMPK KD mice.
Formal Description
Interaction-ID: 2485

drug/chemical compound

AICAR

increases_phosphorylation of

gene/protein

ACACB

in skeletal muscle; in wild-type and AMPK KD mice
Drugbank entries Show/Hide entries for AICAR or ACACB
Comment Both AICAR and muscle contraction increased the phosphorylation of ACC2 to a similar degree in muscle from wild-type and AMPK-KD littermates, although the absolute degree of phosphorylation was modestly reduced in AMPK KD mice.
Formal Description
Interaction-ID: 2486

increases_phosphorylation of

gene/protein

ACACB

in skeletal muscle; in wild-type and AMPK KD mice
Drugbank entries Show/Hide entries for ACACB
Comment AICAR stimulated hormone-sensitive lipase (HSL) Ser-565 phosphorylation in wild-type but not AMPK KD muscle.
Formal Description
Interaction-ID: 2487

drug/chemical compound

AICAR

increases_phosphorylation of

gene/protein

LIPE

in skeletal muscle; in wild-type mice
Drugbank entries Show/Hide entries for AICAR
Comment AICAR stimulated hormone-sensitive lipase (HSL) Ser-565 phosphorylation in wild-type but not AMPK KD muscle.
Formal Description
Interaction-ID: 2488

drug/chemical compound

AICAR

NOT increases_phosphorylation of

gene/protein

LIPE

in skeletal muscle; in AMPK KD mice
Drugbank entries Show/Hide entries for AICAR
Comment Muscle contraction increased HSL Ser-565 phosphorylation to a similar extent in both wild-type and AMPK KD mice.
Formal Description
Interaction-ID: 2489

increases_phosphorylation of

gene/protein

LIPE

in skeletal muscle; in wild-type and AMPK KD mice
Comment AICAR stimulated fatty acid oxidation in both wild-type and AMPK KD extensor digitorum longus (EDL) muscle, but not soleus (SOL) muscle.
Formal Description
Interaction-ID: 2490

drug/chemical compound

AICAR

increases_activity of

in skeletal muscle (EDL); in wild-type and AMPK KD mice
Drugbank entries Show/Hide entries for AICAR
Comment AICAR stimulated fatty acid oxidation in both wild-type and AMPK KD extensor digitorum longus (EDL) muscle, but not soleus (SOL) muscle.
Formal Description
Interaction-ID: 2491

drug/chemical compound

AICAR

NOT increases_activity of

in skeletal muscle (SOL); in wild-type and AMPK KD mice
Drugbank entries Show/Hide entries for AICAR
Comment Isolated extensor digitorum longus (EDL) and soleus (SOL) muscles from wild-type mice were incubated in the presence of etomoxir, an irreversible CPT-1 inhibitor. At rest etomixir had no significant effect on fatty acid oxidation; however, when etomoxir was included during muscle contraction fatty acid oxidation was reduced by 50 and 90% in EDL and SOL muscle, respectively, indicating the critical role of CPT-1 in the regulation of contraction-stimulated fatty acid oxidation.
Formal Description
Interaction-ID: 2494

gene/protein

CPT1B

affects_activity of

in skeletal muscle; during muscle contraction
Comment Muscle contractions performed ex vivo, in situ or during treadmill exercise activate an alternative kinase capable of phosphorylating ACC2 Ser-221 and stimulating fatty acid oxidation in the absence of increases in AMPK activity.
Formal Description
Interaction-ID: 2496

increases_phosphorylation of

gene/protein

ACACB

at Ser221, without activation of AMPK
Drugbank entries Show/Hide entries for ACACB
Comment Extracellular regulated protein-serine kinase (ERK1/2), inhibitor of nuclear factor (NF)-kappaB protein-serine kinase beta (IKKbeta) and protein kinase D (PKD) were predicted to phosphorylate ACC2 at Ser-221, but during in vitro phosphorylation assays only AMPK phosphorylated ACC2.
Formal Description
Interaction-ID: 2512

complex/PPI

AMPK

increases_phosphorylation of

gene/protein

ACACB

in vitro
Drugbank entries Show/Hide entries for ACACB
Comment Extracellular regulated protein-serine kinase (ERK1/2), inhibitor of nuclear factor (NF)-kappaB protein-serine kinase beta (IKKbeta) and protein kinase D (PKD) were predicted to phosphorylate ACC2 at Ser-221, but during in vitro phosphorylation assays only AMPK phosphorylated ACC2.
Formal Description
Interaction-ID: 2513

gene/protein

MAPK3/1

NOT increases_phosphorylation of

gene/protein

ACACB

in vitro
Drugbank entries Show/Hide entries for ACACB
Comment Extracellular regulated protein-serine kinase (ERK1/2), inhibitor of nuclear factor (NF)-kappaB protein-serine kinase beta (IKKbeta) and protein kinase D (PKD) were predicted to phosphorylate ACC2 at Ser-221, but during in vitro phosphorylation assays only AMPK phosphorylated ACC2.
Formal Description
Interaction-ID: 2514

gene/protein

IKBKB

NOT increases_phosphorylation of

gene/protein

ACACB

in vitro
Drugbank entries Show/Hide entries for IKBKB or ACACB
Comment Extracellular regulated protein-serine kinase (ERK1/2), inhibitor of nuclear factor (NF)-kappaB protein-serine kinase beta (IKKbeta) and protein kinase D (PKD) were predicted to phosphorylate ACC2 at Ser-221, but during in vitro phosphorylation assays only AMPK phosphorylated ACC2.
Formal Description
Interaction-ID: 2515

gene/protein

PRKD1

NOT increases_phosphorylation of

gene/protein

ACACB

in vitro
Drugbank entries Show/Hide entries for ACACB
Comment Muscle contractions performed ex vivo, in situ or during treadmill exercise activate an alternative kinase capable of phosphorylating ACC2 Ser-221 and stimulating fatty acid oxidation in the absence of increases in AMPK activity. In summary the results demonstrate that AMPK is not essential for the regulation of fatty acid oxidation by AICAR or muscle contraction.
Formal Description
Interaction-ID: 46070

increases_activity of

without activation of AMPK