High-fat diet and leptin treatment alter skeletal muscle insulin-stimulated phosphatidylinositol 3-kinase activity and glucose transport

Metabolism ◽  
2003 ◽  
Vol 52 (9) ◽  
pp. 1196-1205 ◽  
Author(s):  
Mohenish K Singh ◽  
Adam D Krisan ◽  
Andrew M Crain ◽  
Dale E Collins ◽  
Ben B Yaspelkis
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
High Fat Diet ◽  
Kinase Activity ◽  
Phosphatidylinositol 3 Kinase ◽  
High Fat ◽  
Phosphatidylinositol 3

scholarly journals Lysophosphatidic acid stimulates glucose transport in Xenopus oocytes via a phosphatidylinositol 3′-kinase with distinct properties

1996 ◽  
Vol 316 (1) ◽  
pp. 161-166 ◽  
Author(s):  
Fiona J. THOMSON ◽  
Colin MOYES ◽  
Pamela H. SCOTT ◽  
Robin PLEVIN ◽  
Gwyn W. GOULD
Keyword(s):  
Phosphatidic Acid ◽  
Glucose Transport ◽  
Lysophosphatidic Acid ◽  
Xenopus Oocytes ◽  
Kinase Activity ◽  
Sugar Transport ◽  
Phosphatidylinositol 3 Kinase ◽  
Marked Contrast ◽  
Igf I ◽  
Phosphatidylinositol 3

Lysophosphatidic acid (LPA) stimulated the transport of deoxyglucose into oocytes isolated from Xenopus laevis. This stimulation was accounted for entirely by an increase in the Vmax for transport. Various LPAs with different acyl groups in the sn-1 position and phosphatidic acid stimulated deoxyglucose (deGlc) transport in these cells with a rank order potency of 1-oleoyl-LPA > 1-palmitoyl-LPA > phosphatidic acid = 1-stearoyl-LPA > 1-myristoyl-LPA. The phosphatidylinositol 3´-kinase inhibitor LY294002 completely blocked LPA-stimulated deoxyglucose uptake (IC50 ~2 μM). In marked contrast, wortmannin, which can completely block both insulin-like growth factor-I (IGF-I)-stimulated deGlc uptake in oocytes and phosphatidylinositol 3´-kinase activation at concentrations as low as 20 nM [Gould, Jess, Andrews, Herbst, Plevin and Gibbs (1994) J. Biol. Chem. 269, 26622–26625], was a relatively poor inhibitor of LPA-stimulated deGlc transport, even at concentrations as high as 100 nM. We further show that LPA stimulates phosphatidylinositol 3´-kinase activity(s) that can phosphorylate both phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate, and that this stimulation is inhibited by LY294002 but is relatively insensitive to wortmannin, again in marked contrast to IGF-I-stimulated phosphatidylinositol 3´-kinase activity. Antibodies against the p85 regulatory subunit of phosphatidylinositol 3´-kinase or antiphosphotyrosine antibodies immunoprecipitated IGF-I-stimulated but not LPA-stimulated phosphatidylinositol 3´-kinase activity. We conclude that LPA stimulates glucose uptake in Xenopus oocytes by a mechanism that may involve activation of a form of phosphatidylinositol 3´-kinase that is distinguished from other isoforms by its resistance to wortmannin and by its substrate specificity. Since the LPA-activated form of phosphatidylinositol 3´-kinase is pharmacologically and immunologically distinct from that which is involved in IGF-I-stimulated glucose transport in these cells, we suggest that distinct isoforms of this enzyme are able to function with the same biological effect, at least in the regulation of sugar transport.

Regulation of phosphatidylinositol 3-kinase by insulin in rat skeletal muscle

1993 ◽  
Vol 265 (5) ◽  
pp. E736-E742 ◽  
Author(s):  
K. S. Chen ◽  
J. C. Friel ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Protein Tyrosine Kinase ◽  
Kinase Activity ◽  
Receptor Protein ◽  
Mammalian Skeletal Muscle ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

The presence of phosphatidylinositol 3-kinase (PI 3-kinase) in mammalian skeletal muscle and its response to insulin stimulation were investigated. PI kinase, immunoprecipitated from rat soleus muscle with antibodies directed toward its 85-kDa subunit phosphorylated PI, phosphatidylinositol 4-phosphate [PI(4)P], and phosphatidylinositol 4,5,-bisphosphate [PI(4,5)P2] to yield phosphatidylinositol 3-phosphate [PI(3)P], phosphatidylinositol 3,4,-bisphosphate, and phosphatidylinositol trisphosphate in vitro. PI 3-kinase activity was also immunoprecipitated with antiphosphotyrosine [alpha-Tyr(P)] antibodies and with antibodies raised against IRS-1, a substrate of the insulin receptor protein tyrosine kinase that associates with and activates PI 3-kinase. Incubation of the soleus with insulin in vitro, or injection of insulin into rats in vivo, produced three- to fivefold increases in alpha-Tyr(P)- and alpha-IRS-1-immunoprecipitable PI 3-kinase activity. In nonstimulated soleus muscle, PI 3-kinase activity immunoprecipitated with alpha-IRS-1 or with alpha-Tyr(P) antibodies was evenly distributed between particulate (200,000-g pellet) and soluble fractions. Insulin treatment increased immunoprecipitable PI 5-kinase activity in both fractions, but the increase in alpha-Tyr-(P)-precipitable activity was greater in the particulate fraction, whereas the increase in alpha-IRS-1-precipitable activity was greater in the soluble fraction. In intact soleus muscles incubated with 32PO4, insulin increased the labeling of PI(3)P but did not affect the labeling of PI(4)P or PI(4,5)P2. Activation of PI 3-kinase by insulin was unaffected by prior denervation of the muscle, a manipulation that has been shown to cause both insulin resistance and hypersensitivity in muscles, depending on the parameter measured.(ABSTRACT TRUNCATED AT 250 WORDS)

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