Discovering how diabetes leads to vascular disease

UC Davis Health System Jul 23, 2019

UC Davis Health scientists and physicians have identified a cellular connection between diabetes and blood vessel narrowing that increases risks of serious health conditions such as heart disease and stroke.

The same team previously found that high blood glucose, a hallmark of diabetes, activates an enzyme known as protein kinase A (PKA) that increased calcium channel activity and narrowed blood vessels. Calcium channels are a major focus of cardiovascular disease research, as they are the gatekeepers for calcium ions that relax or widen blood vessels and heart muscle. Both studies were led by Manuel Navedo, professor of pharmacology at UC Davis Health.

“The first outcome was a surprise, since PKA is typically associated with blood vessel widening and wasn’t really on our radar,” Navedo said. “We wanted to understand the molecular processes that created this opposite reaction.”

To find out, Navedo and his team did a series of tests in mice. Those tests showed that in high-glucose conditions, an enzyme known as adenylyl cyclaseone 5—or AC5—launched a string of cellular interactions that activated PKA, followed by the increased calcium-channel activity and narrowed blood vessels they saw in the first study.

The researchers will now test the effects of the AC5 chain reaction on human cells. Their ultimate goal is to find new and effective treatments for the vascular complications of diabetes that can lead to eye, kidney, cerebral, gastrointestinal, and cardiovascular disease.

Cardiologist and study co-author Nipavan Chiamvimonvat is hopeful for this possibility.

“We see every day in our clinics the devastating impact of diabetes on the health and lives of our patients,” said Chiamvimonvat, the Roger Tatarian endowed professor in cardiovascular medicine at UC Davis Health. “Our work brings into much clearer focus how high glucose can damage the vascular system and gives us a new target for blocking its effects.”

More detailed information about the study is available in the UC Davis Health newsroom. The complete study also is available online in The Journal of Clinical Investigation.

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