Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.17 (
CaMKII
)
4,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cardiotrophin-1
(
CT-1
) is a heart-targeting cytokine that is increased in the metabolic syndrome due to overexpression in the adipocytes. The effects of
CT-1
on cardiomyocyte substrate metabolism remain unknown. We therefore determined the effects of
CT-1
on basal and stimulated glucose transport in cardiomyocytes exposed to a low dose (1nM) or a high dose (10nM). Dose-response curves for insulin showed that 1nM
CT-1
reduced insulin responsiveness, while 10nM
CT-1
increased insulin responsiveness. In either condition insulin sensitivity was unaffected. Similarly 1nM
CT-1
reduced the stimulation of glucose transport in response to metabolic stress, induced by the mitochondrial poison oligomycin, while 10nM
CT-1
increased this response. Reduction of stimulated glucose transport by 1nM
CT-1
was associated with overexpression of SOCS-3, a protein known to hinder proximal insulin signaling, and increased phosphorylation of STAT5. In cardiomyocytes exposed to 1nM
CT-1
there was also reduced phosphorylation of Akt and AS160 in response to insulin, and of AMPK in response to oligomycin. Insulin-stimulated glucose transport and signaling were restored by inhibition of STAT5 activity. On the other hand in cardiomyocytes exposed to 10nM
CT-1
there was increased phosphorylation of the AS160 and Akt in response to insulin. Most importantly, basal and oligomycin-stimulated phosphorylation of AMPK was markedly increased in cardiomyocytes exposed to 10nM
CT-1
. The enhancement of basal and stimulated-glucose transport was abolished in cardiomyocytes treated with the
calmodulin-dependent kinase II
(
CaMKII
) inhibitor KN93, and so was AMPK phosphorylation. This suggests that activation of
CaMKII
mediates activation of AMPK by a high dose of
CT-1
independently of metabolic stress. Our results point to a role for
CT-1
in the regulation of myocardial glucose metabolism and implicate entirely separate mechanisms in the inhibitory or stimulatory effects of
CT-1
on glucose transport at low or high concentrations respectively.
...
PMID:Dual effect of the heart-targeting cytokine cardiotrophin-1 on glucose transport in cardiomyocytes. 2327 90
