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Sugar on the brain

Key to diabetes care is managing how the body handles sugar. Glucose is stored as glycogen in tissues throughout the body until it’s called on to provide energy. But little is known about what happens to glycogen stored in the brain.

“What glycogen is doing there and whether it’s metabolically active hasn’t been defined‚ particularly in humans‚” explains Elizabeth Seaquist, M.D., a professor of endocrinology and diabetes at the University of Minnesota. “We haven’t had a way to measure it.”

Seaquist‚ who holds the Pennock Family Land-Grant Chair in Diabetes Research‚ has long suspected that glycogen content in brain tissue may change dramatically in people with type 1 diabetes who suffer from hypoglycemia unawareness. These patients‚ who’ve lost the ability to sense when their blood sugar is low‚ might develop large concentrations of brain glycogen‚ a compensatory response to prolonged periods of low blood sugar. Moreover‚ that glycogen might be metabolized in a unique way.

Two years ago‚ Seaquist and an interdisciplinary team of investigators at the University’s Center for Magnetic Resonance Research—one of the world’s top imaging labs—began to test whether it’s possible to see changes in brain glycogen using high-field magnetic spectroscopy.

They gave healthy subjects a non-radioactive isotope that gets incorporated into glycogen in the brain and then slowly lowered subjects’ blood sugar. As the research participants lay in the hull of the magnet‚ investigators monitored the tagged molecules to see whether brain glycogen changed over time.

The results were clear. Researchers were able to quantify brain glycogen and see marked decreases after hypoglycemia. They were even able to determine how long it took for healthy brains to put the glycogen to use.

“Using spectroscopy‚ we’re able to measure brain glycogen content as we’ve never been able to before‚” Seaquist says.

Now her team is beginning to study patients with type 1 diabetes who have hypoglycemia unawareness‚ comparing their brain glycogen metabolism with the measurements from healthy subjects. The results may reveal more about the conditions necessary for the complication to occur.

“As we know more about how hypoglycemia unawareness happens‚” Seaquist says‚ “we’ll have a leg up on developing therapies to prevent it.”

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