Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the signalling pathways involved in the stimulation of glycogen and fatty acid synthesis by insulin in rat fat cells using wortmannin, an inhibitor of phosphatidylinositol 3-kinase, and rapamycin, which blocks activation of p70 ribosomal S6 protein kinase (p70S6K). Insulin produced a decrease in the activity of glycogen synthase kinase-3 which is likely to be important in the observed stimulation of glycogen synthase. Both of these actions were found to be sensitive to inhibition by wortmannin. Activation of three processes is involved in the stimulation of fatty acid synthesis from glucose by insulin, namely glucose uptake, acetyl-CoA carboxylase and pyruvate dehydrogenase. Whereas wortmannin largely abolished the effects of insulin on glucose utilization and acetyl-CoA carboxylase activity, it was without effect on the stimulation of pyruvate dehydrogenase. Although epidermal growth factor stimulated mitogen-activated protein kinase to a greater extent than insulin, it was unable to mimic the effect of insulin on glycogen synthase, glycogen synthase kinase-3, glucose utilization, acetyl-CoA carboxylase or pyruvate dehydrogenase. Rapamycin also failed to have any appreciable effect on stimulation of these parameters by insulin, although it did block the effect of insulin on p70S6K. We conclude that the activity of phosphatidylinositol 3-kinase is required for the effects of insulin on glycogen synthesis, glucose uptake and acetyl-Co-AN carboxylase, but is not involved in signalling to pyruvate dehydrogenase. Activation of mitogen-activated protein kinase or p70S6K, however, does not appear to be sufficient to bring about the stimulation of fatty acid or glycogen synthesis. Altogether is seems likely that at least four distinct signalling pathways are involved in the effects of insulin on rat fat cells.
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PMID:Multiple signalling pathways involved in the stimulation of fatty acid and glycogen synthesis by insulin in rat epididymal fat cells. 748 1

The metabolic effects of insulin are initiated by the binding of insulin to the extracellular domain of the insulin receptor within the plasma membrane of muscle and adipose and liver cells. The subsequent activation of the intracellular tyrosine protein kinase activity of the receptor leads to autophosphorylation of the receptor as well as phosphorylation of a number of intracellular proteins. This gives rise to the activation of Ras and phosphatidylinositol 3-kinase and hence to the activation of a number of serine/threanine protein kinases. Many of these kinases appear to be arranged in cascades, including a cascade that results in the activation of mitogen-activated protein kinase and another that may result in the activation of protein kinase B, leading to the inhibition of glycogen synthase kinase-3 and the activation of the 70 kiloDalton ribosomal S6 protein kinase (p70 S6 kinase). We have explored the role of these early events in the the stimulation of glycogen, fatty acid, and protein synthesis by insulin in rat epididymal fat cells. Comparisons have been made between the metabolic effects of insulin and those of epidermal growth factor, since these 2 agents have contrasting effects on p70 S6 kinase and mitogen-activated protein kinase. The effects of wortmannin (which inhibits phosphatidylinositol 3-kinase), and rapamycin (which blocks the activation of p70 S6 kinase) have also been studied. These and other studies indicate that the mitogen-activated protein kinase cascade is probably not important in the acute metabolic effects of insulin, but may have a role in the regulation of gene transcription and hence the more long-term effects of insulin. The short-term metabolic effects of insulin appear to involve at least 3 distinct signaling pathways: (1) those leading to increases in glucose transport and the activation of glycogen synthase, acetyl-CoA carboxylase, eukaryotic initiation factor-2B, and phosphodiesterase, which may involve phosphatidylinositol 3-kinase and protein kinase B; (2) those leading to some of the effects of insulin on protein synthesis (formation of eukaryotic initiation factor-4F complex, S6 phosphorylation, and activation of eukaryotic elongation factor-2), which may involve phosphatidylinositol 3-kinase and p70 S6 kinase; and finally, (3) that leading to the activation of pyruvate dehydrogenase, which is unique in apparently not requiring activation of phosphatidylinositol 3-kinase.
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PMID:Multiple signaling pathways involved in the metabolic effects of insulin. 929 55