Powerful antibody-based strategy suggests a new therapeutic approach to diabetes and obesity

Cold Spring Harbor Laboratory ^ | September 29, 2011 | Unknown

[decimon]

Cold Spring Harbor, NY – The work of a team of scientists at Cold Spring Harbor Laboratory (CSHL) led by Professor Nicholas Tonks FRS, suggests a way to overcome one of the major technical obstacles preventing a leading therapeutic target for diabetes and obesity from being addressed successfully by novel drugs.

The target is an enzyme called PTP1B, discovered by Tonks in 1988 and long known to be an important player in the signaling pathway within cells that regulates the response to insulin. Insulin is a hormone that regulates carbohydrate and fat metabolism by spurring cells, particularly in the liver and muscle, to absorb glucose from the bloodstream and store it away for later use.

Insulin exerts its effects by binding to a receptor on the surface of a cell. This receptor then triggers a signaling cascade that involves sequential chemical reactions in which phosphate is added to target proteins by enzymes called kinases. In fact, the insulin receptor is itself a kinase that phosphorylates target proteins on specific tyrosine residues. Phosphorylation of this amino acid in target proteins serves as a switch to regulate function, thereby transmitting the effects of insulin to the machinery of the cell. The effects of the insulin receptor are countered by members of a family of enzymes called the protein tyrosine phosphatases (PTPs), which take the phosphate group back off tyrosine residues in proteins. Of particular importance to the regulation of insulin signaling is the phosphatase PTP1B.

[decimon]

Ping

[sawmill trash]

Interesting

[rdl6989]

Thanks for posting. Bump!

[pyx]

The article's last paragraph also states;

One major technical problem remains. Although these antibodies display the ability to promote insulin signaling, it is extremely difficult to deliver antibodies to the interior of cells as drugs using current biotechnology. Although there are effective antibody therapeutics for other diseases, they tend to be delivered via injection and attach to receptors on the outside of target cells. Therefore, if these new insights about targeting PTP1B are to be of practical use in the near term, Tonks says, a small molecule must be found that has the same effect on PTP1B as the antibodies identified in the team's experiments.

The search for such a molecule has now begun.

Realistically, such molecules could potentially remain hidden, for decades.

[dirtymac]

I knew this! I tried to tell them but no one would listened. The man was just trying to keep me down. You just can’t anyone’s attention without being part of the “in crowd”.

[blueunicorn6]

I thought they fixed this in Canada.