Salk makes major discoveries in diabetes, metabolism

[youtube]http://www.youtube.com/watch?v=bfHP7qRjCwo[/youtube]

By Lynne Friedmann

In 2009, the Center for Nutritional Genomics at the Salk Institute for Biological Studies was founded with the goal of propelling research -- on the molecular level-- of nutrition and its impact on metabolism in diabetes, obesity, cancer, exercise physiology, and lifespan. Just two years later, this collaborative and highly targeted research approach is producing impressive results.

At a press conference on May 12, Salk scientists announced the simultaneous publication of two research studies, in the influential journal

Cell

, disclosing critical discoveries in the area of diabetes and metabolism.

One study revealed how insulin increases fat storage during feeding (news release at

bit.ly/isrZaf

). The other study led to the discovery of a novel “fasting pathway” that points the way to a new class of diabetes drugs that can restore abnormally high blood glucose level to normal (news release at

bit.ly/lqnBON

).

“(These are) the upstream discoveries that ultimately lead to improvements in human health,” said William R. Brody, M.D., Ph.D., president of the Salk Institute.

Together, the studies reveal that a group of enzymes (histone deacetylases or HDACs), plays a central role in controlling the body’s energy balance by getting sugar production rolling when blood glucose levels run low after prolonged periods of fasting or during the night. Without a tightly regulated balance between glucose production in the liver and surplus glucose storage in muscle and fat tissue, blood sugar levels can fluctuate erratically ultimately causing damage to cells and tissues.

“The metabolic system is like a hybrid car,” said Marc R. Montminy, M.D., Ph.D., professor in the Clayton Foundation Laboratories for Peptide Biology, at Salk. “In the daytime we use glucose as high-octane fuel, but at night we switch to the ‘battery,’ which in this case is stored fat."

Unfortunately, in patients with type II diabetes, the liver churns out glucose throughout the day, even when blood sugar levels are high. Salk researchers looked at the ability of class II HDACs to control blood glucose in mouse models of diabetes and found that suppression of all three HDACs simultaneously restored blood glucose levels to almost 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,” said Reuben J. Shaw, Ph.D., a Howard Hughes Medical Institute early career scientist and an assistant professor in the Molecular and Cell Biology Laboratory at Salk.

Recently, many pharmaceutical companies have been developing HDAC inhibitors as anti-cancer drugs, so Shaw speculates that some of these compounds, which may or may not be useful for cancer, could have therapeutic potential for the treatment of insulin resistance and diabetes. If so, this could means new therapies in the clinic in a shorter time period than if drug discovery were starting from scratch.

Lynne Friedmann is a science writer based in Solana Beach

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