Ca2+ effects on glucose transport and fatty acid oxidation in L6 skeletal muscle cell cultures

https://doi.org/10.1016/j.bbrep.2016.01.007Get rights and content
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Highlights

  • Calcium stimulates muscle palmitate oxidation but not glucose transport.

  • Previous studies indicating calcium stimulation of glucose transport required to separate incubation (“post-incubation”).

  • Glucose transport in the post-incubation protocols are independent of glucose as a substrate and show stimulation by caffeine independent of calcium concentration.

  • Calcium stimulation of palmitate oxidation is suppressed by glucose.

  • Glucose uncompetitively suppresses fatty acid oxidation.

Abstract

We examined the effect of Ca2+ on skeletal muscle glucose transport and fatty acid oxidation using L6 cell cultures. Ca2+ stimulation of glucose transport is controversial. We found that caffeine (a Ca2+ secretagogue) stimulation of glucose transport was only evident in a two-part incubation protocol (“post-incubation”). Caffeine was present in the first incubation, the media removed, and labeled glucose added for the second. Caffeine elicited a rise in Ca2+ in the first incubation that was dissipated by the second. This post-incubation procedure was insensitive to glucose concentrations in the first incubation. With a single, direct incubation system (all components present together) caffeine caused a slight inhibition of glucose transport. This was likely due to caffeine induced inhibition of phosphatidylinositol 3-kinase (PI3K), since nanomolar concentrations of wortmannin, a selective PI3K inhibitor, also inhibited glucose transport, and previous investigators have also found this action.

We did find a Ca2+ stimulation (using either caffeine or ionomycin) of fatty acid oxidation. This was observed in the absence (but not the presence) of added glucose. We conclude that Ca2+ stimulates fatty acid oxidation at a mitochondrial site, secondary to malonyl CoA inhibition (represented by the presence of glucose in our experiments). In summary, the experiments resolve a controversy on Ca2+ stimulation of glucose transport by skeletal muscle, introduce an important experimental consideration for the measurement of glucose transport, and uncover a new site of action for Ca2+ stimulation of fatty acid oxidation.

Abbreviations

CaMKK
Calmodulin kinase
PI3K
Phosphatidylinositol 3-kinase
KHB
Krebs Henseleit bicarbonate
CAT I
Carnitine acyl transferase

Keywords

Glucose transport
Fatty acid oxidation
AMP kinase
Skeletal muscle
L6 cells

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