Rottlerin inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes by uncoupling mitochondrial oxidative phosphorylation.

Abstract:

:There is increasing evidence that protein kinase C (PKC) isoforms modulate insulin-signaling pathways in both positive and negative ways. Recent reports have indicated that the novel PKCdelta mediates some of insulin's actions in muscle and liver cells. Many studies use the specific inhibitor rottlerin to demonstrate the involvement of PKCdelta. In this study, we investigated whether PKCdelta might play a role in 3T3-L1 adipocytes. We found that PKCdelta is highly expressed in mouse adipose tissue and increased on 3T3-L1 adipocyte differentiation, and insulin-stimulated glucose transport is blocked by rottlerin. The phosphorylation state and activity of PKCdelta are not altered by insulin, but the protein translocates to membranes following insulin treatment. In contrast to the results with rottlerin, inhibition of PKCdelta activity or expression has no effect on glucose transport in adipocytes, unlike muscle cells. Lastly, we found that rottlerin lowers adenosine triphosphate levels in 3T3-L1 cells by acting as a mitochondrial uncoupler, and this is responsible for the observed inhibition of glucose transport.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Kayali AG,Austin DA,Webster NJ

doi

10.1210/en.2002-220259

subject

Has Abstract

pub_date

2002-10-01 00:00:00

pages

3884-96

issue

10

eissn

0013-7227

issn

1945-7170

journal_volume

143

pub_type

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