Scientists take step forward in understanding how insulin works in cells

by Barbara Hewitt on July 16, 2013

Scientists take step forward in understanding how insulin works in cells

Scientists take step forward in understanding how insulin works in cells

Scientists have discovered a comprehensive blueprint for understanding what goes wrong in diabetes after charting the path of insulin action in cells. In what is being described as a breakthrough study, scientists at the Garvan Institute of Medical Research in Sydney, Australia, believe they are closer to understanding exactly how insulin achieves its task.

‘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,’ said Professor David James. ‘The process is so precise and intricate, and at the same time so monumental in its scope, that it’s truly astounding. Until this study, we did not really appreciate the scale and complexity of insulin regulation,’ he explained.

Colleague Sean Humphrey discovered over 1,500 phosphorylation sites that respond to insulin and shed new light on how one of the most important regulators in the cell, a protein called Akt, is itself regulated. The work has come through the use of the latest analytical devices called mass spectrometers which provide the means of looking into the vastly complex molecular maze that exists in every single cell in the human body.

Quote from : “When Georgetown University neurologist R. Scott Turner, MD, PhD, began enrolling people with mild to moderate Alzheimer’s disease into a nationwide study last year, he expected to find only a handful of participants with undiagnosed glucose intolerance, as all the patients were already under a doctor’s care and those with known diabetes were excluded. But Turner says he was “shocked” by how many study participants were found to have pre-diabetes — a finding that is triggering important questions.”

These powerful devices have opened up a field known as ‘proteomics’, the study of proteins on a very large scale. Proteins represent the working parts of cells, using energy to perform all essential functions such as muscle contraction, heartbeat or even memory. Each cell houses multiple copies of between 10,000 and 12,000 protein types, which communicate with each other using various methods, the most common of which is a process known as ‘phosphorylation’. Phosphate molecules are deliberately added to proteins in order to convey information, or else change the protein’s function.

Each of the protein types in a cell has up to 20 potential ‘phosphorylation sites’, regions to which a phosphate molecule can be added. This pushes the total number of possible cell states from one moment to the next into the billions. The authors discovered 37,248 phosphorylation sites on 5,705 different proteins, 15% of which changed in response to insulin. ‘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 signalling process,’ said James.

‘It’s an important lesson about the usefulness of this technology in allowing us to discover new things about the cell and how it regulates itself,’ he added.

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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