Ca 2+ effects on glucose transport and fatty acid oxidation in L6 skeletal muscle cell cultures

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.

Astrocytic metabolic switch is a novel etiology for Cocaine and HIV-1 Tat-mediated neurotoxicity

“…Next, we assessed whether increased mitochondrial respiration in astrocytes exposed to rTat and cocaine is mediated by an increase in the rate of [Ca 2+ ] m uptake. It has been shown that cocaine/ionomycin treatment stimulates mitochondrial metabolism in a Ca 2+ -dependent manner 36 . Since we hypothesized MCU-mediated Ca 2+ uptake as a nodal point for the astrocyte metabolic switching during rTat/cocaine stimulation, we assessed if blocking MCU-mediated [Ca 2+ ] m uptake in astrocytes could prevent the decreased lactate and increased Acetyl-CoA.…”

“…Accordingly, we showed FAO to play a significant role in sustaining inflammatory responses in the CNS and therapeutic interventions targeting FAO could well be appreciated. Cocaine exposure is expected to increase intracellular Ca 2+ transients through G-protein coupled receptors (GPCR) stimulation 36 . Likewise, Tat is known to cause over activation of NMDA receptors and intracellular Ca 2+ -dependent damage to oligodendrocytes and myelin 46 , 47 .…”

Amelioration of insulin resistance using the additive effect of ferulic acid and resveratrol on vesicle trafficking for skeletal muscle glucose metabolism

“…It is known that cytosolic calcium would stimulate glycogen phosphorylase which in turn activate glycogenolysis and tricarboxylic acid cycle (Balu, Ouyang, Parakhia, Pitake, & Ochs, 2016). Conventional protein kinase C (cPKC) and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) are potential targets of Ca 2+ , leading to increase in glucose uptake (Huang & Czech, 2007).…”

The role of calcium metabolism dysregulation in the pathogenesis of cardiovascular diseases

“…] i в адипоцитах и других клетках-мишенях инсулина может повышать резистентность к инсулину путем фосфорилирования транспортера глюкозы 4 типа и других субстратов, чувствительных к инсулину, что снижает эффективность инсулинопосредованного поглощения глюкозы [18].…”