scholarly journals The phosphatidylinositol 3-kinase inhibitor, wortmannin, inhibits insulin-induced activation of phosphatidylcholine hydrolysis and associated protein kinase C translocation in rat adipocytes

1996 ◽  
Vol 313 (3) ◽  
pp. 1039-1046 ◽  
Author(s):  
Mary L. STANDAERT ◽  
Antoine AVIGNON ◽  
Kouji YAMADA ◽  
Gautam BANDYOPADHYAY ◽  
Robert V. FARESE
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Glucose Transport ◽  
Phospholipase D ◽  
Kinase Inhibitor ◽  
Phosphatidylinositol 3 Kinase ◽  
Rat Adipocytes ◽  
Kinase C ◽  
Pkc Β

We questioned whether phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase C (PKC) function as interrelated signalling mechanisms during insulin action in rat adipocytes. Insulin rapidly activated a phospholipase D that hydrolyses phosphatidylcholine (PC), and this activation was accompanied by increases in diacylglycerol and translocative activation of PKC-α and PKC-β in the plasma membrane. Wortmannin, an apparently specific PI 3-kinase inhibitor, inhibited insulin-stimulated, phospholipase D-dependent PC hydrolysis and subsequent translocation of PKC-α and PKC-β to the plasma membrane. Wortmannin did not inhibit PKC directly in vitro, or the PKC-dependent effects of phorbol esters on glucose transport in intact adipocytes. The PKC inhibitor RO 31-8220 did not inhibit PI 3-kinase directly or its activation in situ by insulin, but inhibited both insulin-stimulated and phorbol ester-stimulated glucose transport. Our findings suggest that insulin acts through PI 3-kinase to activate a PC-specific phospholipase D and causes the translocative activation of PKC-α and PKC-β in plasma membranes of rat adipocytes.

scholarly journals Increased flux through the hexosamine biosynthesis pathway inhibits glucose transport acutely by activation of protein kinase C

1997 ◽  
Vol 324 (3) ◽  
pp. 981-985 ◽  
Author(s):  
Anthony FILIPPIS ◽  
Stella CLARK ◽  
Joseph PROIETTO
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Glucose Transport ◽  
High Glucose ◽  
Biosynthesis Pathway ◽  
Rat Adipocytes ◽  
Kinase C ◽  
Hexosamine Biosynthesis ◽  
Hexosamine Biosynthesis Pathway

The hexosamine biosynthesis pathway and protein kinase C (PKC) activation mediate hyperglycaemia-induced impaired glucose transport, but the relative role of each pathway is unknown. Following a 2 h preincubation of rat adipocytes in the presence of either high glucose (30 mM) plus insulin (0.7 nM) or glucosamine (3 mM), both high glucose and glucosamine inhibited subsequent basal and insulin-stimulated glucose transport, measured at 5.0 mM glucose. Azaserine, an inhibitor of the enzyme glutamine:fructose-6-phosphate aminotransferase, abolished the effect of high glucose, but not that of glucosamine. Ro-31-8220, an inhibitor of PKC, reversed the effects of both high glucose and glucosamine, suggesting that flux through the hexosamine biosynthesis pathway impaired glucose transport acutely by activating PKC. Both high glucose and glucosamine caused a 3-fold increase in PKC activity; this effect of high glucose, but not that of glucosamine, was partially decreased by azaserine. Neither high glucose nor glucosamine altered basal or insulin-stimulated plasma membrane GLUT1 levels, whereas both treatments decreased basal, but not insulin-stimulated, GLUT4 levels. Azaserine abolished the effect of high glucose, but not that of glucosamine, on basal plasma membrane GLUT4 levels. Ro-31-8220, which returned glucose transport to control values, caused a further decrease in plasma membrane GLUT4 levels. It is concluded that, in rat adipocytes, an acute increase in flux through the hexosamine biosynthesis pathway inhibits glucose transport by activation of PKC.

Different pathways of degradation of SP-A and saturated phosphatidylcholine by alveolar macrophages

2000 ◽  
Vol 279 (1) ◽  
pp. L91-L99 ◽  
Author(s):  
Aldo Baritussio ◽  
Antonella Alberti ◽  
Decio Armanini ◽  
Federica Meloni ◽  
Daniela Bruttomesso
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Alveolar Macrophages ◽  
Surfactant Protein ◽  
Phosphatidylinositol 3 Kinase ◽  
Lysosomal Compartment ◽  
Lysosomal Ph ◽  
Kinase C ◽  
Stimulation Of

Alveolar macrophages degrade surfactant protein (SP) A and saturated phosphatidycholine [dipalmitoylphosphatidylcholine (DPPC)]. To clarify this process, using rabbit alveolar macrophages, we analyzed the effect of drugs known to affect phagocytosis, pinocytosis, clathrin-mediated uptake, caveolae, the cytoskeleton, lysosomal pH, protein kinase C, and phosphatidylinositol 3-kinase (PI3K) on the degradation of SP-A and DPPC. We found the following: 1) SP-A binds to the plasma membrane, is rapidly internalized, and then moves toward degradative compartments. Uptake could be clathrin mediated, whereas phagocytosis, pinocytosis, or the use of caveolae are less likely. An intact cytoskeleton and an acidic milieu are necessary for the degradation of SP-A. 2) Stimulation of protein kinase C increases the degradation of SP-A. 3) PI3K influences the degradation of SP-A by regulating both the speed of internalization and subsequent intracellular steps, but its inhibition does not prevent SP-A from reaching the lysosomal compartment. 4) The degradation of DPPC is unaffected by most of the treatments able to influence the degradation of SP-A. Thus it appears that DPPC is degraded by alveolar macrophages through mechanisms very different from those utilized for the degradation of SP-A.

scholarly journals Protein Kinase C-ζ as a Downstream Effector of Phosphatidylinositol 3-Kinase during Insulin Stimulation in Rat Adipocytes

1997 ◽  
Vol 272 (48) ◽  
pp. 30075-30082 ◽  
Author(s):  
Mary L. Standaert ◽  
Lamar Galloway ◽  
Purushotham Karnam ◽  
Gautam Bandyopadhyay ◽  
Jorge Moscat ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Insulin Stimulation ◽  
Rat Adipocytes ◽  
Downstream Effector ◽  
Kinase C ◽  
Phosphatidylinositol 3

scholarly journals Lactosylceramide-enriched glycosphingolipid signaling domain mediates superoxide generation from human neutrophils

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1454-1464 ◽  
Author(s):  
Kazuhisa Iwabuchi ◽  
Isao Nagaoka
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Superoxide Generation ◽  
Kinase C ◽  
Signaling Domain

This study is focused on the functional significance of neutrophil lactosylceramide (LacCer)–enriched microdomains, which are involved in the initiation of a signal transduction pathway leading to superoxide generation. Treatment of neutrophils with anti-LacCer antibody, T5A7 or Huly-m13, induced superoxide generation from the cells, which was blocked by PP1, a Src kinase inhibitor; wortmannin, a phosphatidylinositol-3 kinase inhibitor; SB203580, a p38 mitogen-activated protein kinase (MAPK) inhibitor; and H7, an inhibitor for protein kinase C. When promyelocytic leukemia HL-60 cells were differentiated into neutrophilic lineage by dimethyl sulfoxide (DMSO) treatment, they acquired superoxide-generating activity but did not respond to anti-LacCer antibodies. Density gradient centrifugation revealed that LacCer and Lyn were recovered in detergent-insoluble membrane (DIM) of neutrophils and DMSO-treated HL-60 cells. However, immunoprecipitation experiments indicated that LacCer was associated with Lyn in neutrophils but not in DMSO-treated HL-60 cells. Interestingly, T5A7 induced the phosphorylation of Lyn in neutrophils but not in DMSO-treated HL-60 cells. Moreover, T5A7 induced the phosphorylation of p38 MAPK in neutrophils. T5A7-induced Lyn phosphorylation in neutrophil DIM fraction was significantly enhanced by cholesterol depletion or sequestration with methyl-β-cyclodextrin or nystatin. Collectively, these data suggest that neutrophils are characterized by the presence of cell surface LacCer-enriched glycosphingolipid signaling domain coupled with Lyn and that the ligand binding to LacCer induces the activation of Lyn, which may be suppressibly regulated by cholesterol, leading to superoxide generation through the phosphatidylinositol-3 kinase–, p38 MAPK–, and protein kinase C–dependent signal transduction pathway.

Sulfonylureas activate glucose transport and protein kinase C in rat adipocytes

Metabolism ◽  
1991 ◽  
Vol 40 (2) ◽  
pp. 196-200 ◽  
Author(s):  
R.V. Farese ◽  
T. Ishizuka ◽  
M.L. Standaert ◽  
D.R. Cooper
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Glucose Transport ◽  
Rat Adipocytes ◽  
Kinase C
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