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Protein kinase C epsilon deletion in adipose tissue, but not in liver, improves glucose tolerance

Brandon, AE, Liao, BM, Diakanastasis, B, Parker, BL, Raddatz, K, McManus, SA, O'Reilly, L, Kimber, E, van der Kraan, AG, Hancock, D, Henstridge, DC ORCID: 0000-0003-4988-767X, Meikle, PJ, Cooney, GJ, James, DE, Reibe, S, Febbraio, MA, Biden, TJ and Schmitz-Peiffer, C 2019 , 'Protein kinase C epsilon deletion in adipose tissue, but not in liver, improves glucose tolerance' , Cell Metabolism, vol. 29, no. 1 , 183-191.e7 , doi: 10.1016/j.cmet.2018.09.013.

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Protein kinase C epsilon (PKCɛ) activation in the liver is proposed to inhibit insulin action through phosphorylation of the insulin receptor. Here, however, we demonstrated that global, but not liver-specific, deletion of PKCɛ in mice protected against diet-induced glucose intolerance and insulin resistance. Furthermore, PKCɛ-dependent alterations in insulin receptor phosphorylation were not detected. Adipose-tissue-specific knockout mice did exhibit improved glucose tolerance, but phosphoproteomics revealed no PKCɛ-dependent effect on the activation of insulin signaling pathways. Altered phosphorylation of adipocyte proteins associated with cell junctions and endosomes was associated with changes in hepatic expression of several genes linked to glucose homeostasis and lipid metabolism. The primary effect of PKCɛ on glucose homeostasis is, therefore, not exerted directly in the liver as currently posited, and PKCɛ activation in this tissue should be interpreted with caution. However, PKCɛ activity in adipose tissue modulates glucose tolerance and is involved in crosstalk with the liver.

Item Type: Article
Authors/Creators:Brandon, AE and Liao, BM and Diakanastasis, B and Parker, BL and Raddatz, K and McManus, SA and O'Reilly, L and Kimber, E and van der Kraan, AG and Hancock, D and Henstridge, DC and Meikle, PJ and Cooney, GJ and James, DE and Reibe, S and Febbraio, MA and Biden, TJ and Schmitz-Peiffer, C
Keywords: adipose tissue, glucose intolerance, high-fat diet, insulin resistance, liver, phosphoproteomics, PKC epsilon, protein kinase C, type 2 diabetes, cholesterol ester, diacylglycerol, glucose, insulin, insulin receptor, phospholipid, sphingolipid, male
Journal or Publication Title: Cell Metabolism
Publisher: Cell Press
ISSN: 1550-4131
DOI / ID Number: 10.1016/j.cmet.2018.09.013
Copyright Information:

Copyright 2018 Elsevier Inc.

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