Contribution of the serine kinase c-Jun N-terminal kinase (JNK) to oxidant-induced insulin resistance in isolated rat skeletal muscle

Fernando R. Santos, Maggie K. Diamond-Stanic, Mujalin Prasannarong, Erik J Henriksen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The specific and direct contribution of the stress-activated serine kinase c-Jun N-terminal kinase (JNK) in the development of oxidative stress-induced insulin resistance of the glucose transport system in mammalian skeletal muscle is not fully understood. We assessed the specific role of JNK in the development of insulin resistance caused by in vitro exposure of rat soleus muscle to low levels (30-40 μM) of the oxidant hydrogen peroxide (H2O2) for up to 6h. Oxidant exposure caused significant (p < 0.05) decreases in insulin-stimulated glucose transport activity (up to 42%) and Akt Ser 473 phosphorylation (up to 67%), and increased (up to 74%) phosphorylation (Thr183/Tyr185) of JNK1 and JNK2/3 isoforms. Importantly, insulin-stimulated glucose transport activity in the presence of H2O2 was moderately improved with the selective JNK inhibitor SP600125. These results indicate that activation of the serine kinase JNK contributes, at least in part, to oxidative stress-induced insulin resistance in isolated mammalian skeletal muscle.

Original languageEnglish (US)
Pages (from-to)231-236
Number of pages6
JournalArchives of Physiology and Biochemistry
Volume118
Issue number5
DOIs
StatePublished - Dec 2012

Fingerprint

JNK Mitogen-Activated Protein Kinases
Protein-Serine-Threonine Kinases
Oxidants
Insulin Resistance
Skeletal Muscle
Glucose
Oxidative Stress
Phosphorylation
Insulin
Hydrogen Peroxide
Protein Isoforms

Keywords

  • Akt serine phosphorylation
  • Glucose transport
  • Hydrogen peroxide
  • Soleus muscle
  • SP600125

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Contribution of the serine kinase c-Jun N-terminal kinase (JNK) to oxidant-induced insulin resistance in isolated rat skeletal muscle. / Santos, Fernando R.; Diamond-Stanic, Maggie K.; Prasannarong, Mujalin; Henriksen, Erik J.

In: Archives of Physiology and Biochemistry, Vol. 118, No. 5, 12.2012, p. 231-236.

Research output: Contribution to journalArticle

@article{92011ce8d3a246b3981f5dc5dc799ada,
title = "Contribution of the serine kinase c-Jun N-terminal kinase (JNK) to oxidant-induced insulin resistance in isolated rat skeletal muscle",
abstract = "The specific and direct contribution of the stress-activated serine kinase c-Jun N-terminal kinase (JNK) in the development of oxidative stress-induced insulin resistance of the glucose transport system in mammalian skeletal muscle is not fully understood. We assessed the specific role of JNK in the development of insulin resistance caused by in vitro exposure of rat soleus muscle to low levels (30-40 μM) of the oxidant hydrogen peroxide (H2O2) for up to 6h. Oxidant exposure caused significant (p < 0.05) decreases in insulin-stimulated glucose transport activity (up to 42{\%}) and Akt Ser 473 phosphorylation (up to 67{\%}), and increased (up to 74{\%}) phosphorylation (Thr183/Tyr185) of JNK1 and JNK2/3 isoforms. Importantly, insulin-stimulated glucose transport activity in the presence of H2O2 was moderately improved with the selective JNK inhibitor SP600125. These results indicate that activation of the serine kinase JNK contributes, at least in part, to oxidative stress-induced insulin resistance in isolated mammalian skeletal muscle.",
keywords = "Akt serine phosphorylation, Glucose transport, Hydrogen peroxide, Soleus muscle, SP600125",
author = "Santos, {Fernando R.} and Diamond-Stanic, {Maggie K.} and Mujalin Prasannarong and Henriksen, {Erik J}",
year = "2012",
month = "12",
doi = "10.3109/13813455.2012.713366",
language = "English (US)",
volume = "118",
pages = "231--236",
journal = "Archives of Physiology and Biochemistry",
issn = "1381-3455",
publisher = "Informa Healthcare",
number = "5",

}

TY - JOUR

T1 - Contribution of the serine kinase c-Jun N-terminal kinase (JNK) to oxidant-induced insulin resistance in isolated rat skeletal muscle

AU - Santos, Fernando R.

AU - Diamond-Stanic, Maggie K.

AU - Prasannarong, Mujalin

AU - Henriksen, Erik J

PY - 2012/12

Y1 - 2012/12

N2 - The specific and direct contribution of the stress-activated serine kinase c-Jun N-terminal kinase (JNK) in the development of oxidative stress-induced insulin resistance of the glucose transport system in mammalian skeletal muscle is not fully understood. We assessed the specific role of JNK in the development of insulin resistance caused by in vitro exposure of rat soleus muscle to low levels (30-40 μM) of the oxidant hydrogen peroxide (H2O2) for up to 6h. Oxidant exposure caused significant (p < 0.05) decreases in insulin-stimulated glucose transport activity (up to 42%) and Akt Ser 473 phosphorylation (up to 67%), and increased (up to 74%) phosphorylation (Thr183/Tyr185) of JNK1 and JNK2/3 isoforms. Importantly, insulin-stimulated glucose transport activity in the presence of H2O2 was moderately improved with the selective JNK inhibitor SP600125. These results indicate that activation of the serine kinase JNK contributes, at least in part, to oxidative stress-induced insulin resistance in isolated mammalian skeletal muscle.

AB - The specific and direct contribution of the stress-activated serine kinase c-Jun N-terminal kinase (JNK) in the development of oxidative stress-induced insulin resistance of the glucose transport system in mammalian skeletal muscle is not fully understood. We assessed the specific role of JNK in the development of insulin resistance caused by in vitro exposure of rat soleus muscle to low levels (30-40 μM) of the oxidant hydrogen peroxide (H2O2) for up to 6h. Oxidant exposure caused significant (p < 0.05) decreases in insulin-stimulated glucose transport activity (up to 42%) and Akt Ser 473 phosphorylation (up to 67%), and increased (up to 74%) phosphorylation (Thr183/Tyr185) of JNK1 and JNK2/3 isoforms. Importantly, insulin-stimulated glucose transport activity in the presence of H2O2 was moderately improved with the selective JNK inhibitor SP600125. These results indicate that activation of the serine kinase JNK contributes, at least in part, to oxidative stress-induced insulin resistance in isolated mammalian skeletal muscle.

KW - Akt serine phosphorylation

KW - Glucose transport

KW - Hydrogen peroxide

KW - Soleus muscle

KW - SP600125

UR - http://www.scopus.com/inward/record.url?scp=84869420795&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84869420795&partnerID=8YFLogxK

U2 - 10.3109/13813455.2012.713366

DO - 10.3109/13813455.2012.713366

M3 - Article

VL - 118

SP - 231

EP - 236

JO - Archives of Physiology and Biochemistry

JF - Archives of Physiology and Biochemistry

SN - 1381-3455

IS - 5

ER -