Activation of phosphatidylinositol-3 kinase, AMP-activated kinase and Akt substrate-160 kDa by trans-10, cis-12 conjugated linoleic acid mediates skeletal muscle glucose uptake

2013 ◽  
Vol 24 (2) ◽  
pp. 445-456 ◽  
Author(s):  
Suresh K. Mohankumar ◽  
Carla G. Taylor ◽  
Linda Siemens ◽  
Peter Zahradka
Keyword(s):  
Skeletal Muscle ◽  
Linoleic Acid ◽  
Glucose Uptake ◽  
Conjugated Linoleic Acid ◽  
Phosphatidylinositol 3 Kinase ◽  
Skeletal Muscle Glucose Uptake ◽  
Phosphatidylinositol 3

scholarly journals Oxidative stress stimulates skeletal muscle glucose uptake through a phosphatidylinositol 3-kinase-dependent pathway

2008 ◽  
Vol 294 (5) ◽  
pp. E889-E897 ◽  
Author(s):  
Yasuki Higaki ◽  
Toshio Mikami ◽  
Nobuharu Fujii ◽  
Michael F. Hirshman ◽  
Katsuhiro Koyama ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Intracellular Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
Maximal Increase ◽  
Skeletal Muscle Glucose Uptake ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Phosphatidylinositol 3

We determined the acute effects of oxidative stress on glucose uptake and intracellular signaling in skeletal muscle by incubating muscles with reactive oxygen species (ROS). Xanthine oxidase (XO) is a superoxide-generating enzyme that increases ROS. Exposure of isolated rat extensor digitorum longus (EDL) muscles to Hx/XO (Hx/XO) for 20 min resulted in a dose-dependent increase in glucose uptake. To determine whether the mechanism leading to Hx/XO-stimulated glucose uptake is associated with the production of H2O2, EDL muscles from rats were preincubated with the H2O2 scavenger catalase or the superoxide scavenger superoxide dismutase (SOD) prior to incubation with Hx/XO. Catalase treatment, but not SOD, completely inhibited the increase in Hx/XO-stimulated 2-deoxyglucose (2-DG) uptake, suggesting that H2O2 is an intermediary leading to Hx/XO-stimulated glucose uptake with incubation. Direct H2O2 also resulted in a dose-dependent increase in 2-DG uptake in isolated EDL muscles, and the maximal increase was threefold over basal levels at a concentration of 600 μmol/l H2O2. H2O2-stimulated 2-DG uptake was completely inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, but not the nitric oxide inhibitor N G-monomethyl-l-arginine. H2O2 stimulated the phosphorylation of Akt Ser473 (7-fold) and Thr308 (2-fold) in isolated EDL muscles. H2O2 at 600 μmol/l had no effect on ATP concentrations and did not increase the activities of either the α1 or α2 catalytic isoforms of AMP-activated protein kinase. These results demonstrate that acute exposure of muscle to ROS is a potent stimulator of skeletal muscle glucose uptake and that this occurs through a PI3K-dependent mechanism.

Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is an AMPK target participating in contraction-stimulated glucose uptake in skeletal muscle

2013 ◽  
Vol 455 (2) ◽  
pp. 195-206 ◽  
Author(s):  
Yang Liu ◽  
Yu-Chiang Lai ◽  
Elaine V. Hill ◽  
Donatienne Tyteca ◽  
Sarah Carpentier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Ampk Activation ◽  
Glut4 Translocation ◽  
Skeletal Muscle Glucose Uptake ◽  
Stimulation Of ◽  
Phosphatidylinositol 3

We propose that PIKfyve activity is required for the stimulation of skeletal muscle glucose uptake by contraction/AMPK activation. AMPK-induced phosphorylation of PIKfyve at Ser307 could favour its translocation to endosomes for PtdIns(3,5)P2 production, which facilitates GLUT4 translocation.

ATP-sensitive K+ channel-mediated glucose uptake is independent of IRS-1/phosphatidylinositol 3-kinase signaling

2003 ◽  
Vol 285 (6) ◽  
pp. E1289-E1296 ◽  
Author(s):  
Kohtaro Minami ◽  
Mizuo Morita ◽  
Atsunori Saraya ◽  
Hideki Yano ◽  
Yasuo Terauchi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Knockout Mice ◽  
Skeletal Muscles ◽  
K Channel ◽  
Phosphatidylinositol 3 Kinase ◽  
Double Knockout ◽  
Phosphatidylinositol 3

We previously found that disruption of Kir6.2-containing ATP-sensitive K+ (Katp) channels increases glucose uptake in skeletal muscle, but the mechanism is not clear. In the present study, we generated knockout mice lacking both Kir6.2 and insulin receptor substrate-1 (IRS-1). Because IRS-1 is the major substrate of insulin receptor kinase, we expected disruption of the IRS-1 gene to reduce glucose uptake in Kir6.2 knockout mice. However, the double-knockout mice do not develop insulin resistance or glucose intolerance. An insulin tolerance test reveals the glucose-lowering effect of exogenous insulin in double-knockout mice and in Kir6.2 knockout mice to be similarly enhanced compared with wild-type mice. The basal 2-deoxyglucose uptake rate in skeletal muscle of double-knockout mice is increased similarly to the rate in Kir6.2 knockout mice. Accordingly, disruption of the IRS-1 gene affects neither systemic insulin sensitivity nor glucose uptake in skeletal muscles of Kir6.2-deficient mice. In addition, no significant changes were observed in phosphatidylinositol 3-kinase (PI3K) activity and its downstream signal in skeletal muscle due to lack of the Kir6.2 gene. Disruption of Kir6.2-containing Katp channels clearly protects against IRS-1-associated insulin resistance by increasing glucose uptake in skeletal muscles by a mechanism separate from the IRS-1/PI3K pathway.

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