Journal article

Effects of PKB/Akt inhibitors on insulin-stimulated lipogenesis and phosphorylation state of lipogenic enzymes in white adipose tissue

Nusrat Hussain, Sheng-Ju Chuang, Manuel Johanns, Didier Vertommen, Gregory R Steinberg, Bruce E Kemp, Mark H Rider

BIOCHEMICAL JOURNAL | PORTLAND PRESS LTD | Published : 2020

Abstract

We investigated acute effects of two allosteric protein kinase B (PKB) inhibitors, MK-2206 and Akti-1/2, on insulin-stimulated lipogenesis in rat epididymal adipocytes incubated with fructose as carbohydrate substrate. In parallel, the phosphorylation state of lipogenic enzymes in adipocytes and incubated epididymal fat pads was monitored by immunoblotting. Preincubation of rat epididymal adipocytes with PKB inhibitors dose-dependently inhibited the following: insulin-stimulated lipogenesis, increased PKB Ser473 phosphorylation, increased PKB activity and decreased acetyl-CoA carboxylase (ACC) Ser79 phosphorylation. In contrast, the effect of insulin to decrease the phosphorylation of pyruva..

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Grants

Awarded by Interuniversity Poles of Attraction Belgian Science Policy


Awarded by Fund for Medical Scientific Research (FNRS, Belgium)


Awarded by Canadian Institutes of Health Research


Awarded by Australian Research Council


Awarded by Australian Research Council (NHMRC)


Funding Acknowledgements

N.H. was supported by the Interuniversity Poles of Attraction Belgian Science Policy (P6/28 and P7/13) and by UCLouvain. The work was funded by the Interuniversity Poles of Attraction Belgian Science Policy (P6/28 and P7/13), by the Directorate General Higher Education and Scientific Research, French Community of Belgium, and by the Fund for Medical Scientific Research (FNRS, Belgium) grant numbers 3.4518.11 and T.0008.15. GRS is supported by a Canada Research Chair and the J Bruce Duncan Endowed Chair in Metabolic Diseases and program grants from the Canadian Institutes of Health Research (201709FDN-CEBA-116200) and Diabetes Canada. B.E.K. is a National Health and Medical Research Council of Australia Fellow supported by the Australian Research Council (DP170101196 and NHMRC, APP1085460).