CIDeRplusGeneral Information:
| Id: | 496 |
| Diseases: |
Diabetes mellitus, type II
- [OMIM]
Insulin resistance |
| Mus musculus | |
| BTO:0000011 3T3-L1 cell | |
| article | |
| Reference: | Gauthier MS et al.(2008) AMP-activated protein kinase is activated as a consequence of lipolysis in the adipocyte: potential mechanism and physiological relevance. J. Biol. Chem. 283 [PMID: 18390901] |
Interaction Information:
| Comment | Incubation of 3T3-L1 adipocytes with a beta-adrenergic agonist (isoproterenol) and an adenylyl cyclase activator (forskolin) caused a 20-fold increase in lipolysis. |
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Formal Description Interaction-ID: 2386 |
drug/chemical compound increases_activity of process |
| Drugbank entries | Show/Hide entries for Isoproterenol |
| Comment | Incubation of 3T3-L1 adipocytes with a beta-adrenergic agonist (isoproterenol) and an adenylyl cyclase activator (forskolin) caused a 20-fold increase in lipolysis. |
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Formal Description Interaction-ID: 2420 |
drug/chemical compound increases_activity of process |
| Comment | Isoproterenol and forskolin also activated AMPK as reflected by increases in the phosphorylation of its alpha-subunit at Thr-172 and of its downstream target ACC at Ser-79. |
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Formal Description Interaction-ID: 2421 |
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| Drugbank entries | Show/Hide entries for Isoproterenol |
| Comment | Isoproterenol and forskolin also activated AMPK as reflected by increases in the phosphorylation of its alpha-subunit at Thr-172 and of its downstream target ACC at Ser-79. |
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Formal Description Interaction-ID: 2422 |
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| Comment | Isoproterenol and forskolin also activated AMPK as reflected by increases in the phosphorylation of its alpha-subunit at Thr-172 and of its downstream target ACC at Ser-79. |
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Formal Description Interaction-ID: 2423 |
drug/chemical compound increases_phosphorylation of gene/protein AMPK alpha chain |
| Comment | Isoproterenol and forskolin also activated AMPK as reflected by increases in the phosphorylation of its alpha-subunit at Thr-172 and of its downstream target ACC at Ser-79. |
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Formal Description Interaction-ID: 2424 |
drug/chemical compound increases_phosphorylation of gene/protein AMPK alpha chain |
| Drugbank entries | Show/Hide entries for Isoproterenol |
| Comment | Isoproterenol and forskolin also activated AMPK as reflected by increases in the phosphorylation of its alpha-subunit at Thr-172 and of its downstream target ACC at Ser-79. |
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Formal Description Interaction-ID: 2425 |
drug/chemical compound increases_phosphorylation of gene/protein |
| Drugbank entries | Show/Hide entries for Isoproterenol or ACACA |
| Comment | Isoproterenol and forskolin also activated AMPK as reflected by increases in the phosphorylation of its alpha-subunit at Thr-172 and of its downstream target ACC at Ser-79. |
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Formal Description Interaction-ID: 2426 |
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| Drugbank entries | Show/Hide entries for ACACA |
| Comment | Incubation of the cells with the phosphodiesterase inhibitor IBMX also stimulated lipolysis and increased AMPK and ACC phosphorylation. Because the phosphodiesterase catalyzes the conversion of cAMP to AMP, this essentially rules out this source of AMP as a major cause of AMPK activation during lipolysis. |
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Formal Description Interaction-ID: 2427 |
drug/chemical compound increases_activity of process |
| Comment | Incubation of the cells with the phosphodiesterase inhibitor IBMX also stimulated lipolysis and increased AMPK and ACC phosphorylation. Because the phosphodiesterase catalyzes the conversion of cAMP to AMP, this essentially rules out this source of AMP as a major cause of AMPK activation during lipolysis. |
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Formal Description Interaction-ID: 2428 |
drug/chemical compound increases_phosphorylation of gene/protein AMPK alpha chain |
| Comment | Incubation of the cells with the phosphodiesterase inhibitor IBMX also stimulated lipolysis and increased AMPK and ACC phosphorylation. Because the phosphodiesterase catalyzes the conversion of cAMP to AMP, this essentially rules out this source of AMP as a major cause of AMPK activation during lipolysis. |
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Formal Description Interaction-ID: 2429 |
drug/chemical compound increases_phosphorylation of gene/protein |
| Drugbank entries | Show/Hide entries for ACACA |
| Comment | Orlistat, a general lipase inhibitor, inhibited the ability of the three lipolytic agents (isoproterenol, forskolin, and IBMX) agents to stimulate lipolysis, and it had a similar inhibitory effect on AMPK activation. |
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Formal Description Interaction-ID: 2438 |
drug/chemical compound decreases_activity of process |
| Drugbank entries | Show/Hide entries for Orlistat |
| Comment | Forskolin caused a 50-fold increase in intracellular cAMP levels. |
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Formal Description Interaction-ID: 2439 |
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| Drugbank entries | Show/Hide entries for cAMP |
| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2440 |
drug/chemical compound increases_activity of complex/PPI Protein kinase A |
| Drugbank entries | Show/Hide entries for Isoproterenol |
| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2441 |
drug/chemical compound increases_activity of complex/PPI Protein kinase A |
| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2442 |
drug/chemical compound increases_activity of complex/PPI Protein kinase A |
| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2443 |
drug/chemical compound increases_phosphorylation of gene/protein AMPK alpha chain |
| Drugbank entries | Show/Hide entries for Isoproterenol |
| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2444 |
drug/chemical compound increases_phosphorylation of gene/protein AMPK alpha chain |
| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2445 |
drug/chemical compound increases_phosphorylation of gene/protein AMPK alpha chain |
| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2446 |
drug/chemical compound increases_phosphorylation of gene/protein |
| Drugbank entries | Show/Hide entries for Isoproterenol |
| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2447 |
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| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2448 |
drug/chemical compound increases_phosphorylation of gene/protein |
| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2449 |
drug/chemical compound increases_phosphorylation of gene/protein |
| Drugbank entries | Show/Hide entries for Isoproterenol or CREB1 |
| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2450 |
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| Drugbank entries | Show/Hide entries for CREB1 |
| Comment | The three lipolytic agents (isoproterenol, forskolin, and IBMX) augmented cAMP-dependent protein kinase (PKA) activity as reflected by their ability to increase the abundance of phosphorylated serine and threonine residues of PKA substrates (AMPK alpha chain, LKB1 at Ser-431, CREB cAMP-response element-binding protein at Ser-133). |
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Formal Description Interaction-ID: 2451 |
drug/chemical compound increases_phosphorylation of gene/protein |
| Drugbank entries | Show/Hide entries for CREB1 |
| Comment | 3T3-L1 adipocytes were treated with cAMP-inducing agents (isoproterenol, forskolin, and isobutylmethylxanthine), which stimulate lipolysis and activate AMPK. When lipolysis was partially inhibited with the general lipase inhibitor orlistat, AMPK activation by these agents was also partially reduced, but the increases in cAMP levels and cAMP-dependent protein kinase (PKA) activity were unaffected. |
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Formal Description Interaction-ID: 2452 |
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| Drugbank entries | Show/Hide entries for Orlistat or cAMP |
| Comment | Forskolin caused a decrease in ATP levels, no significant change in ADP, and an increase in AMP, resulting in an about 4-fold increase in the AMP:ATP ratio compared with control cells. |
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Formal Description Interaction-ID: 2454 |
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| Comment | Isoproterenol treatment of 3T3-L1 adipocytes for 1 h led to a 25% increase in reactive oxygen species (ROS) generation. |
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Formal Description Interaction-ID: 2466 |
drug/chemical compound increases_quantity of drug/chemical compound Reactive oxygen species |
| Drugbank entries | Show/Hide entries for Isoproterenol |
| Comment | 3T3-L1 adipocytes were incubated with the competitive inhibitor of AMPK, compound C, this increased ROS production in 3T3-L1 adipocytes in a dose-dependent manner. |
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Formal Description Interaction-ID: 2467 |
drug/chemical compound Compound C increases_quantity of drug/chemical compound Reactive oxygen species |
| Comment | 1 h of isoproterenol stimulation in the presence of compound C resulted in a further 5-fold increase in ROS production. |
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Formal Description Interaction-ID: 2468 |
drug/chemical compound affects_quantity of drug/chemical compound Reactive oxygen species |
| Drugbank entries | Show/Hide entries for Isoproterenol |
| Comment | Inhibition of AMPK activity with compound C increases ROS production and lipolysis. |
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Formal Description Interaction-ID: 2469 |
drug/chemical compound Compound C decreases_activity of complex/PPI AMPK |
| Comment | In conclusion, the results indicate that activation of AMPK in adipocytes by cAMP-inducing agents is a consequence of lipolysis and not of PKA activation. They suggest that AMPK activation in this setting is caused by an increase in the AMP:ATP ratio that appears to be due, at least in part, to the acylation of fatty acids. Finally, this AMPK activation appears to restrain the energy depletion and oxidative stress caused by lipolysis. |
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Formal Description Interaction-ID: 2471 |
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| Drugbank entries | Show/Hide entries for cAMP |
| Comment | Orlistat, a general lipase inhibitor, inhibited the ability of the three lipolytic agents (isoproterenol, forskolin, and IBMX) agents to stimulate lipolysis, and it had a similar inhibitory effect on AMPK activation. |
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Formal Description Interaction-ID: 12438 |
drug/chemical compound decreases_activity of complex/PPI AMPK |
| Drugbank entries | Show/Hide entries for Orlistat |
| Comment | 3T3-L1 adipocytes were treated with cAMP-inducing agents (isoproterenol, forskolin, and isobutylmethylxanthine), which stimulate lipolysis and activate AMPK. When lipolysis was partially inhibited with the general lipase inhibitor orlistat, AMPK activation by these agents was also partially reduced, but the increases in cAMP levels and cAMP-dependent protein kinase (PKA) activity were unaffected. |
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Formal Description Interaction-ID: 12440 |
drug/chemical compound NOT affects_activity of complex/PPI Protein kinase A |
| Drugbank entries | Show/Hide entries for Orlistat |
| Comment | Forskolin caused a decrease in ATP levels, no significant change in ADP, and an increase in AMP, resulting in an about 4-fold increase in the AMP:ATP ratio compared with control cells. |
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Formal Description Interaction-ID: 12769 |
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| Comment | Forskolin caused a decrease in ATP levels, no significant change in ADP, and an increase in AMP, resulting in an about 4-fold increase in the AMP:ATP ratio compared with control cells. |
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Formal Description Interaction-ID: 12770 |
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| Comment | 1 h of isoproterenol stimulation in the presence of compound C resulted in a further 5-fold increase in ROS production. |
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Formal Description Interaction-ID: 12771 |
drug/chemical compound Compound C affects_quantity of drug/chemical compound Reactive oxygen species |
| Comment | Inhibition of AMPK activity with compound C increases ROS production and lipolysis. |
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Formal Description Interaction-ID: 12772 |
drug/chemical compound Compound C increases_quantity of drug/chemical compound Reactive oxygen species |
| Comment | Inhibition of AMPK activity with compound C increases ROS production and lipolysis. |
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Formal Description Interaction-ID: 12773 |
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