Enzyme Discovery May Lead to New Diabetes Medication

Researchers at the Salk Institute for Biological Studies have discovered a mechanism that stimulates glucose production in the liver in response to a drop in blood sugar. Histone deacetylasses (HDACs) are a group of enzymes that respond to what researchers call “fasting signals”.

 

Fasting signals kick in after long periods without food, such as overnight. HDACs are situated in liver cells, usually outside of the nucleus. The Salk researchers discovered that they move rapidly into the cell in response to fasting signals, and turn on the genes that produce glucose.

 

After a meal, the hormone insulin normally prompts cells to store glucose for future fuel, and turns off the liver’s sugar production to avoid blood glucose from getting too high. Many people with type 2 diabetes have insulin resistance, a condition in which the body no longer responds properly to insulin, allowing the liver to continue manufacturing glucose, resulting in high blood sugar.

 

Currently, most type 2 diabetics are prescribed an oral diabetes medication called metformin (marketed as Glucophage XR) to help control their blood sugar levels. “Metformin is originally derived from a plant found in Western Europe called ‘French lilac’ or ‘Goat’s Rue because goats don’t like to eat it, explains scientist Reuben Shaw, Ph.D., “They steered clear of the plant because it contains a compound that acts naturally to lower blood glucose in animals that eat it to prevent them from eating it again.”

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Shaw researched metformin to find out how it helped insulin to control blood sugar.  He discovered it binds to AMPK, a metabolic regulating enzyme which blocks glucose production in the liver. A graduate student in his laboratory, Maria Mihhaylova, then delved into targets of AMPKs relevant to diabetes, eventually focusing on a family of HDACs called class II HDACs.

 

In collaboration with two other labs, Mihhaylova discovered that HDACs only controlled glucose synthesizing enzymes in response to the fasting hormone glucagon. “In response to the glucagon, chemical modifications on class II HDACs are removed, and they can translocate into the [liver cell] nucleus”, she explains.

 

The team went on to perform tests on mice with dramatic results -  suppression of HDACs restored blood glucose levels to near normal in four different models of type 2 diabetes. “These exciting results show that drugs that inhibit the activity of class II HDACs may be worthwhile to be pursued as potential diabetes drugs,” says Shaw.

 

The search for a new and improved diabetes medication may get a boost from current cancer research – prescription drug companies have been developing HDAC inhibitors as anti-cancer drugs. Shaw hopes that some of the compounds they have developed could have therapeutic potential for the treatment of insulin resistance and diabetes, whether or not they are effective against cancer.

no.

just remember, any herb that causes significant medical results has JUST as many side effects as prescription meds. not necessarily any safer, and usually NOT tested. some things cause kidney or liver damage, and it is better to know before you take it!

metformin usually is ok if you ease into the dose slowly enough. to me it was worth it. for the first month felt like a stomach full of rocks.

no way you will get MORE results from the herb!

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