Type 2 diabetes reversed with new drug in mouse study – The San Diego Union-Tribune

Type 2 diabetes has been reversed in mice with a new, orally available drug, according to a study led by San Diego scientists. The study suggests a path for developing human therapies based on the drug.

The drug protected mice from high-fat induced diabetes without affecting body weight, according to the study. It also reversed signs of the disease in mice who already had it.

Type 2 diabetes is caused by insulin resistance. While the pancreatic islets still make insulin, the hormone doesnt work as well. Cells sense insulin through receptors, which become less effective in this type of diabetes.

Scientists led by Nunzio Bottini of the La Jolla Institute for Allergy & Immunology countered insulin resistance by designing a drug that restored the effectiveness of insulin receptors.

The drug inhibits an enzyme called a low-molecular-weight protein tyrosine phosphatase, or LMPTP. Its part of a family of enzymes that inactivates the insulin receptor. By inhibiting this particular enzyme in the liver, insulin receptor effectiveness was restored.

Our findings suggest that LMPTP activity plays a key role in the development of insulin resistance and that LMPTP inhibitors would be beneficial for treating type 2 diabetes, the study stated.

While the role of protein tyrosine phosphatases in Type 2 diabetes has been known for years, many enzymes in this family perform other functions,and drugs against these enzymes may also affect other targets. The drug arising from the research is exceptionally selective in its activity, the researchers said, reducing the chance of side effects.

The study was published Monday in Nature Chemical Biology. It can be found at j.mp/diabetestyr. Bottini was senior author. Stephanie M. Stanford, also of the La Jolla institute, was first author. Other local authors are from UC San Diego and Sanford Burnham Prebys Medical Discovery Institute.

We envision that the information we collected about its mechanism of action and binding mode will pave the way for development of LMPTP inhibitors suitable for therapeutic testing in human diabetes, the study stated.

Since LMPTP has also been proposed to promote heart failure and tumor growth, such inhibitors are predicted to have a wide range of therapeutic applications.

Stroke, Alzheimers disease, cognitive decline and polycystic ovary syndrome are among the other diseases that have been linked to insulin resistance.

A researcher not involved in the study told New Scientist that the research is promising.

The elegant studies here provide proof of concept that targeting LMPTP in the liver improves glucose control and liver insulin signalling in animals, Daniel Drucker, a senior investigator at the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada, said in the New Scientist article.

Researchers started their search by screening 364,168 small-molecule compounds from the National Institutes of Health Molecular Libraries Small Molecule Repository. They found three hits, or molecules active against the target. One was selected for further study because of its potency and specificity.

Using medicinal chemistry, the researchers tweaked the molecule to make it more potent. One of the resulting compounds was then tested in live mice.

The La Jolla Institute for Allergy and Immunology and Sanford Burnham Medical Discovery Institute hold a pending patent on the discovery.

The researchers were funded by grants from the National Institutes of Health and the American Diabetes Association.

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Type 2 diabetes reversed with new drug in mouse study - The San Diego Union-Tribune