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Insight into the dazzling impact of insulin in cells
Date:5/21/2013

nsulin.

"Until this study, we did not really appreciate the scale and complexity of insulin regulation," said lab leader Professor David James.

"When insulin is released from the pancreas after we eat, it travels to cells and initiates a cascade of protein phosphorylation, literally millions of interactions, some instantaneous, some taking minutes or hours. The process is so precise and intricate, and at the same time so monumental in its scope, that it's truly astounding."

Sean Humphrey, who undertook the mass spectrometry work, discovered over 1,500 phosphorylation sites that respond to insulin, and described the process as "eye opening".

"When you consider that phosphorylation is only one type of signaling acetylation and methylation are other forms you begin to understand the kind of complexity that faces us," he said.

In addition to cataloguing the phosphoproteome of the fat cell, the authors discovered novel regulation of a protein called 'SIN1', key to our understanding of the chain of events that occurs during insulin signaling. They have also described the mechanisms by which SIN1 influences other influential proteins within the cell, in particular one known as Akt.

"Sean's study has shed new light on how one of the most important regulators in the cell a protein called Akt is itself regulated," said Professor James.

"Akt not only plays a role in diabetes, but also in cancer and other diseases, and the discovery of SIN1 phosphorylation gives us useful new insights into how Akt actually functions in a cell."

"These large scale approaches are providing us with new levels of understanding of human biology that we would never have anticipated. Without the mass spectrometer, we could not have discovered the importance of SIN1 phosphorylation in the overall insulin signaling process."

"It's an important lesson about the usefulness of this technology in allowing us to discov
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Contact: Alison Heather
a.heather@garvan.org.au
61-292-958-128
Garvan Institute of Medical Research
Source:Eurekalert

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