Treatment For Type 2 Diabetes
A study led by researchers at the Salk Institute for Biological Studies discovered a new type 2 diabetes treatment target represented by a pair of molecules that control hepatic glucose production, IP3 and calcineurin. The study, published in the journal Nature, was conducted on mice and had promising results, as stated Professor Marc Montminy, Salk’s head of Clayton Foundation Laboratories for Peptide Biology. He is convinced that if he manages to control the activity of both molecules, he can control blood glucose levels. Such discoveries of novel treatments able to fight diabetes are necessary due to the high incidence of diabetes and the cost that this disease has. In U.S. alone, 26 million people are currently diagnosed with diabetes and it is estimated that nearly 80 million more are at risk of developing diabetes in the near future.
During a research focused on glucose metabolism, Professor Marc Montminy and his team found that glucagon, an antagonist hormone of insulin, also secreted by the pancreas, activates the genetic switch (CRTC2), which increases blood glucose. Insulin, on the other hand, inhibits CRTC2, and lowers blood glucose. The researchers also found that in type 2 diabetes the genetic switch is turned on too strong, and insulin cannot inactivate CRTC2. In addition, they discovered how glucagon acts at the level of molecular receptors, IP3, which are found on the surface of liver cells. Through signaling pathways involving calcium and calcineurin, glucagon determines the liver to produce glucose during fasting. Scientists also found that IP3 receptor and calcineurin are found in increased numbers in the liver of diabetic patients. The new therapeutic target are just these two molecules, receptor IeP3 and calcineurin. If researchers manage to reduce the activity of these two molecules, then hepatic glucose production could be fully controlled.
Diabetes is a chronic condition characterized by hyperglycemia, ie increased blood glucose levels. Blood glucose level is controlled by insulin, a hormone produced by the pancreas. Insulin works by introducing glucose into cells, hence lowers blood glucose levels. When insulin is insufficient, glucose can not enter cells and hyperglycemia ensues. First, hyperglycemia is asymptomatic, but in time lead to serious complications such as blindness, atherosclerosis (narrowing of blood vessels), neuropathy (nerve damage) and nephropathy (impaired renal function). Symptoms can be caused by complications or triad: polyuria (frequent urination), polydipsia (thirst continues), polyphagia (increased appetite).
Current treatment of diabetes includes biguanides, drugs that reduce hepatic glucose output and increases glucose uptake in peripheral tissues, thiazolidinediones. There are also used meglitinides, sulfonylureas, alpha-glucoside inhibitors, etc.. The most used drug, however, is metformin, a biguanide. Metformin is the only oral antidiabetic medicine that does not cause weight gain. However it should be mentioned that metformin should be used carefully in people with liver or renal dysfunction.