Navigation Links
Insight into the dazzling impact of insulin in cells

Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.

The breakthrough study, conducted by Sean Humphrey and Professor David James from Sydney's Garvan Institute of Medical Research, is now published in the early online edition of the prestigious journal Cell Metabolism.

First discovered in 1921, the insulin hormone plays a very important role in the body because it helps us lower blood sugar after a meal, by enabling the movement of sugar from the blood into cells. Until now, although scientists have understood the purpose of insulin at a broad level, they have struggled to understand exactly how it achieves its task.

The latest analytical devices called mass spectrometers now provide the tool that has been missing the means of looking into the vastly complex molecular maze that exists in every single cell in the human body.

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.

"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 discover new things about the cell and how it regulates itself."


Contact: Alison Heather
Garvan Institute of Medical Research

Related biology news :

1. New insights into cloud formation
2. Research on flavanols and procyanidins provides new insights into how these phytonutrients may positively impact human health
3. New insight into mechanisms behind autoimmune diseases suggests a potential therapy
4. Discovery offers insight into treating viral stomach flu
5. Fine-scale analysis of the human brain yields insight into its distinctive composition
6. Chimpanzee ground nests offer new insight into our ancestors descent from the trees
7. Battle of the sexes offers evolutionary insights
8. Analysis of speed of Greenland glaciers gives new insight for rising sea level
9. Mice with big brains provide insight into brain regeneration and developmental disorders
10. Maps of Miscanthus genome offer insight into grass evolution
11. Songbirds learning hub in brain offers insight into motor control
Post Your Comments:
(Date:11/17/2015)... Paris from 17 th ... Paris from 17 th until 19 th ... leader, has invented the first combined scanner in the world ... scanning surface. Until now two different scanners were required: one ... both on the same surface. This innovation is an ...
(Date:11/16/2015)... Nov 16, 2015  Synaptics Inc. (NASDAQ: ... solutions, today announced expansion of its TDDI product ... touch controller and display driver integration (TDDI) solutions ... These new TDDI products add to the previously-announced ... TD4302 (WQHD resolution), and TD4322 (FHD resolution) solutions. ...
(Date:11/11/2015)... Minn. , Nov. 11, 2015   MedNet Solutions ... entire spectrum of clinical research, is pleased to announce that ... in Clinical Trials (PCT) event, to be held November ... be able to view live demonstrations of iMedNet ... and learn how iMedNet has been able to ...
Breaking Biology News(10 mins):
(Date:12/1/2015)... ... December 01, 2015 , ... ... scientifically backed, age-defying products, is featured as the cover story and throughout ... and unrivaled opportunities that Nerium provides. Success from Home magazine routinely features ...
(Date:12/1/2015)... , Dec. 1, 2015 Cepheid (Nasdaq: ... participation at the Piper Jaffray Healthcare Conference in ... the Company is reaffirming its outlook for the fourth ... in addition to discussing longer term business model expectations. ... Executive Officer.  "We continue to be the fastest growing ...
(Date:12/1/2015)... Texas (PRWEB) , ... December 01, 2015 , ... ... annual global meeting this month and Dr. J. Kyle Mathews will ... This includes the new single site hysterectomy. , An experienced urogynecologist, founder of ...
(Date:12/1/2015)... , December 1, 2015 ... of the  "2016 U.K. Virology and Bacteriology ... for 100 Tests, Supplier Shares by Test, ... to their offering.  --> ... "2016 U.K. Virology and Bacteriology Testing Market: ...
Breaking Biology Technology: