Inhibition of AMPK activity in response to insulin in adipocytes - involvement of AMPK pS485, PDEs and cellular energy levels.

Inhibition of AMPK activity in response to insulin in adipocytes - involvement of AMPK pS485, PDEs and cellular energy levels. Am J Physiol Endocrinol Metab. 2020 Jul 14;: Authors: Kopietz F, Rupar K, Berggreen C, Säll J, Vertommen D, Degerman E, Rider M, Göransson O Abstract Insulin resistance in obesity and type 2 diabetes (T2D) 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, if the S485 phosphorylation is required for insulin-induced inhibition of AMPK, or if other mechanisms underlie the reduced kinase activity, is not known. In order to investigate this, primary rat adipocytes were transduced with a recombinant adenovirus encoding AMPK-WT or a non-phosphorylatable AMPK S485A mutant. AMPK activity measurements by western blotting 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 f...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research