The discovery bodes well for sufferers of this disease, which seems to be on the increase, particularly in the western world. Although the molecular mechanisms behind Type 2 diabetes are not fully known, it is thought the increase is due to the excessive calorie-rich diets and more sedentary nature of typical Western lifestyles.
Two experimental drugs, GW501516 and GW0742, were tested in the study, which also focused on receptors in the muscle cells called peroxsome proliferators-activated delta receptors (PFAARd). The receptors regulate the enzymes involved in the cell's metabolism and energy production.
The trials demonstrate that the two drugs bind to PFAARd, which triggers a series of reactions within the cells. This helped to boost glucose absorption into the cells. By specifically blocking certain processes in the cells, 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.
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.
"The discoveries are important as one of the problems with insulin therapy for patients with Type 2 diabetes is 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 PFAARd 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.
Diabetes represents a large and growing unmet medical need. In the United States, more than 11 million people are diagnosed with diabetes, and a similar number of patients are thought to be undiagnosed. Disease prevalence is on the rise, as are epidemic rates of obesity. Diabetes is associated with severe comoroid conditions including cardiovascular disease, blindness, limb loss and kidney failure and is among the most costly diseases.
According to IMS data, the global market for oral diabetes treatments exceeded $4.5 billion (€3.4 billion) in 2004. The global market for insulin approximated $3 billion in 2003.
The new study, entitled: "Direct Activation of Glucose Transport in Primary Human Myotubes After Activation of Peroxisome Proliferator-Activated Receptor delta" is published in the scientific journal Diabetes (April 2005).