Lehrman, Unger receive High Impact/High Risk support

By Kristen Holland Shear / Feb. 19-28, 2011

Two faculty members have received funding to establish projects through UT Southwestern’s High Impact/High Risk Research Program.

The projects are led by Dr. Mark Lehrman, professor of pharmacology, and Dr. Roger Unger, professor of internal medicine in the Touchstone Diabetes Center.

Dr. Roger Unger (left) and Dr. Young Lee

The UT Southwestern program emphasizes research that has the potential to greatly influence the science or practice of medicine even though there is also a substantial risk of failure. Grant recipients receive support for a year to test a hypothesis and determine whether the idea has promise.

With the latest approvals, 32 faculty members have received grants through the program since it was established in 2001.

Dr. Lehrman, a glycobiologist, is investigating the idea that glycogen — when found in cells outside the liver, muscle or brain — has an entirely different purpose than fuel regulation.

Glycogen can come from ingested carbohydrates and is stored in large amounts in the liver and skeletal muscle until the body needs it. Muscle glycogen fuels people’s muscles during exercise and is known for providing the energy source for the fight-or-flight response. Glycogen stored in the liver is important for maintaining glucose “fuel” levels in the blood. Stored glycogen is also an important energy source for brain function.

Though most glycogen research involves its function in the liver, brain or muscles, researchers have also identified small amounts of glycogen in other parts of the body such as skin cells. Dr. Lehrman proposes an entirely new physiological role for this glycogen and has suggested the term “glycogus” to highlight the distinction between the glycogen in other types of cells and the glycogen found in the liver, brain and muscles.

“We propose that while glycogen found in the liver, brain and muscle responds to a classical type of signaling known as PKA signaling, we are finding that glycogus seems to respond to a different signaling system altogether. And instead of providing glucose for fuel, glycogus appears to provide glucose for assembling glycoconjugates, which are crucially important carbohydrates linked to proteins and lipids,” Dr. Lehrman said. “We think we’ve identified a dichotomy between textbook glycogen and the actions of glycogus in cells that don’t have a major role in regulating fuel metabolism.”

Dr. Unger will complete a short-term clinical trial that aims to determine whether adding the brain hormone somatostatin to standard insulin therapy might help rein in the tumultuous blood-sugar levels of type 1 (insulin-dependent) diabetics.

Somatostatin has been shown to suppress the secretion of glucagon, a hormone produced by the pancreas that raises blood sugar levels in healthy individuals.

Glucagon normally is released when the glucose level in the blood is low. In insulin deficiency situations, however, glucagon levels are inappropriately high and cause the liver to release excessive amounts of glucose into the bloodstream. This action is opposed by insulin, which tells the body’s cells to remove sugar from the bloodstream.

“The idea is to see if we can get an acute suppression of glucagon, followed by a decrease in glucose,” said Dr. Unger, whose laboratory previously found that insulin’s benefit resulted from its suppression of glucagon.

The trial will take one to two weeks and participants will spend at least the first few days under constant supervision. Dr. Unger said the hope is that the findings “will improve the quality of life for patients with type 1 diabetes.”

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Dr. Unger holds the Touchstone/West Distinguished Chair in Diabetes Research.

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