Novel Anti-Diabetic Mechanism Discovered
According to the America Diabetes Association, there are nearly 24 million adults and children in the United States suffering from one complication or the other of Type 2 diabetes. This disorder is closely related to obesity.
In fact, excess body fat is the most problematic risk factor among all the factors of metabolic syndrome, responsible for increasing the risk of diabetes and heart ailments.
The formation of fat cells in the body is regulated by a protein called the PPARy. There are some research drugs which target the fat regulating ability of this protein inorder to treat diabetes. It is because obesity causes changes in this substance leading to a decrease in the production of an insulin-sensitizing protein (adiponectin), and hence insulin resistance.
But unfortunately, all the presently available drugs which target PPARy also increase fat while trying to inhibit insulin resistance. This is one of the unwanted long-term side effects of these drugs.
A new study published on July 22, 2010, in the journal Nature (Volume 466, Issue 7304) has found a mechanism by which an improved generation of anti-diabetic drugs can be developed. They are potent insulin sensitizers but do not cause fat generation.
The study was supported by the National Institutes of Health and the Deutsche Forschungsgemeinschaft (DFG). This article tries to gain further insight on this topic.
The Anti-diabetic Drug Mechanism:
The process by which reprogramming of genes controlled by PPARγ protein occurs is called phosphorylation. It happens when an enzyme molecule called the cdk5 kinase gets added to this protein. Compounds which activate the enzyme cdk5 kinase are called the agonists.
The scientists discovered that these agonists interact with PPARγ protein in such a manner that it can cause reversed phosphorylation process. This will lead to improved production of adiponectin, which is an insulin-sensitizing protein.
Agonists are either full or partial. The study found that full agonists strongly interacted with a PPARy protein only to generate more fat but be less effective in stopping phosphorylation. When compared to full agonists, partial agonists were better at reversing phosphorylation. A particular partial agonist, MRL-24, interacted with the protein by targeting a potentially critical region of it associated with the phosphorylation process.
It was supposed that during the interaction, partial agonist MRL24 caused mutation in the receptors at the cdk5 kinase site, leading to reverse phosphorylation. As expected, blocking phosphorylation lead to increased production of adiponectin for increased insulin sensitivity, in experimental animals.
Moreover, high fat diets were found to activate the cdk5 kinase and initiate phosphorylation. The conclusion can be extended on humans too.
Drugs similar to MRL24 partial agonist in action, can now be developed to deal with the cdk5 kinase receptor and reverse the phosphorylation process.