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Drugs targeted at muscle cells


Can be of use in the treatment of diabetes patients with insulin resistance

Type 2 diabetes is a clinical disease characterised by disruption to the metabolism of glucose and lipids as well as to the production of and physiological reactions to insulin. These disruptions are partly due to a reduced absorption of glucose in the cells that form the body’s fat and muscle tissue. Now scientists at Karolinska Institutet have established that a type of drug targeted at receptors in the muscle cells increases the metabolism and absorption of glucose, making it a potential tool in the treatment of diabetes.

These new findings were published recently in the scientific journal Diabetes. The study has been partly financed with two EU grants from the sixth framework programme (EUGENE2 and EXGENESIS), which were recently awarded to an international network of researchers that includes the authors of the article.

The molecular mechanisms behind Type 2 diabetes are not fully known, but both hereditary and environmental factors are thought to contribute to its development. The prevalence and number of new cases of Type 2 diabetes are steadily increasing in the West, owing, it is thought, to the excessive calorie-rich diets and more sedentary nature of typical Western lifestyles.

The receptors in the muscle cells that were studied are called peroxisome proliferators-activated delta receptors (PFAARä) and they reside in the nucleus where they regulate a large number of enzymes involved in the cell’s metabolism and energy production. Using human muscle cells cultivated in vitro, the researchers were able to show that drugs that bind to PFAARä increase the absorption of glucose in the muscle cells. The two experimental drugs tested in the study were GW501516 and GW0742. The trials demonstrate that the two drugs bind to PFAARä, which triggers a series of reactions within the cells. This, in turn, helps to boost glucose absorption into the cells. By specifically blocking certain processes in the cells, the scientists were also able to show that the effects of the drugs resembled those caused by physical activity. They were also able to show that this was not the result of any effect on insulin signals.

"The discoveries we’ve made are important bearing in mind that one of the problems with insulin therapy for patients with Type 2 diabetes is that they eventually develop a resistance to the insulin and no longer respond to the treatment," say Anna Krook and Juleen Zierath, two of the KI research scientists behind the study. "The PFAARä drugs we have studied, on the other hand, have a direct effect on the cultivated muscle cells and act independently of insulin metabolism. If we can show that the drugs are also effective on living patients, it means that they could one day be used for the treatment of patients who have developed insulin resistance."

Sabina Bossi | EurekAlert!
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