E4orf1 induction in adipose tissue promotes insulin-independent signaling in the adipocyte.

ABSTRACT:

Background/purpose

Type 2 diabetes remains a worldwide epidemic with major pathophysiological changes as a result of chronic insulin resistance. Insulin regulates numerous biochemical pathways related to carbohydrate and lipid metabolism.

Methods

We have generated a novel mouse model that allows us to constitutively activate, in an inducible fashion, the distal branch of the insulin signaling transduction pathway specifically in adipocytes.

Results

Using the adenoviral 36 E4orf1 protein, we chronically stimulate locally the Ras-ERK-MAPK signaling pathway. At the whole body level, this leads to reduced body-weight gain under a high fat diet challenge. Despite overlapping glucose tolerance curves, there is a reduced requirement for insulin action under these conditions.

SUBMITTER: Kusminski CM 

PROVIDER: S-EPMC4588421 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature