Inhibition of AMPK activity in response to insulin in adipocytes: involvement of AMPK pS485, PDEs, and cellular energy levels
| Autor: | Kaja Rupar, Mark H. Rider, Didier Vertommen, Olga Göransson, Eva Degerman, Johanna Säll, Franziska Kopietz, Christine Berggreen |
|---|---|
| Přispěvatelé: | UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/PHOS - Protein phosphorylation |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Glycerol medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Adipose tissue 030209 endocrinology & metabolism AMP-Activated Protein Kinases Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Insulin resistance Endocrinology Adenosine Triphosphate AMP-activated protein kinase Internal medicine Physiology (medical) medicine Adipocytes Animals Insulin Kinase activity Phosphorylation Protein kinase A biology Chemistry Phosphoric Diester Hydrolases Fatty Acids AMPK medicine.disease Adenosine Monophosphate Rats Diabetes and Metabolism 030104 developmental biology Fatty acid synthesis Mutation biology.protein pS485 Energy Metabolism Proto-Oncogene Proteins c-akt |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism, Vol. 319, no. 3, p. E459-E471 (2020) |
| ISSN: | 1522-1555 |
| Popis: | Insulin resistance in obesity and type 2 diabetes has been shown to be associated with decreased de novo fatty acid (FA) synthesis in adipose tissue. It is known that insulin can acutely stimulate FA synthesis in adipocytes; however, the mechanisms underlying this effect are unclear. The rate-limiting step in FA synthesis is catalyzed by acetyl-CoA carboxylase (ACC), known to be regulated through inhibitory phosphorylation at S79 by the AMP-activated protein kinase (AMPK). Previous results from our laboratory showed an inhibition of AMPK activity by insulin, which was accompanied by PKB-dependent phosphorylation of AMPK at S485. However, whether the S485 phosphorylation is required for insulin-induced inhibition of AMPK or other mechanisms underlie the reduced kinase activity is not known. To investigate this, primary rat adipocytes were transduced with a recombinant adenovirus encoding AMPK-WT or a nonphosphorylatable AMPK S485A mutant. AMPK activity measurements by Western blot analysis and in vitro kinase assay revealed that WT and S485A AMPK were inhibited to a similar degree by insulin, indicating that AMPK S485 phosphorylation is not required for insulin-induced AMPK inhibition. Further analysis suggested an involvement of decreased AMP-to-ATP ratios in the insulin-induced inhibition of AMPK activity, whereas a possible contribution of phosphodiesterases was excluded. Furthermore, we show that insulin-induced AMPK S485 phosphorylation also occurs in human adipocytes, suggesting it to be of an importance yet to be revealed. Altogether, this study increases our understanding of how insulin regulates AMPK activity, and with that, FA synthesis, in adipose tissue. |
| Databáze: | OpenAIRE |
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