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New target for the treatment of diabetes

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A new potential target for the treatment of type 2 diabetes was reported on Nov. 13, 2013 in the journal Nature. The new study identifies two small molecules that disrupt the activity of a protein involved in regulating glucose. This disruption results in normalized blood glucose levels.

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An estimated 6.4% of adults in Connecticut (that's ~189,000 adults) have been diagnosed with diabetes (2010 data). There are nearly 26 million Americans with diagnosed diabetes (2011 data). Diabetes is a major cause of heart disease and stroke and the 7th leading cause of death in the U.S.

Keeping glucose levels balanced is a vital and complex process. If this balance is disturbed, disorders such as hyperglycemia (high levels of glucose in the blood) and type 2 diabetes can develop. A critical enzyme involved in lowering glucose levels in the blood is glucokinase (GK). The activity of GK is regulated by a number of factors, including GK activators and an inhibitory GK regulatory protein (GKRP).

Current treatments for type 2 diabetes target GK activators. However, these treatments can lower glucose levels too far. Additionally, some people become desensitized to this treatment. This new study examined GKRP to see if it would be an effective alternative target.

The study identified two potent small molecules that could increase GK activity in the liver. These two compounds were then tested in diabetic animals and were found to decrease blood glucose levels. The compounds did not decrease blood glucose levels in non-diabetic control animals, indicating that blocking GKRP does not lower glucose levels below normal levels, as many current treatments sometimes do.

This study was performed in an animal model of diabetes and more studies are needed. But, this new class of glucose-lowering agents holds promise for improving glucose metabolism in patients with diabetes.

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