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Traffic. 2013 Mar;14(3):259-73. doi: 10.1111/tra.12035. Epub 2013 Jan 18.

Novel systems for dynamically assessing insulin action in live cells reveals heterogeneity in the insulin response.

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1
Diabetes and Obesity Research Program, The Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.

Abstract

Regulated GLUT4 trafficking is a key action of insulin. Quantitative stepwise analysis of this process provides a powerful tool for pinpointing regulatory nodes that contribute to insulin regulation and insulin resistance. We describe a novel GLUT4 construct and workflow for the streamlined dissection of GLUT4 trafficking; from simple high throughput screens to high resolution analyses of individual vesicles. We reveal single cell heterogeneity in insulin action highlighting the utility of this approach - each cell displayed a unique and highly reproducible insulin response, implying that each cell is hard-wired to produce a specific output in response to a given stimulus. These data highlight that the response of a cell population to insulin is underpinned by extensive heterogeneity at the single cell level. This heterogeneity is pre-programmed within each cell and is not the result of intracellular stochastic events.

PMID:
23252720
DOI:
10.1111/tra.12035
[Indexed for MEDLINE]
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