UC Davis researchers identify how diabetes increases the risk of vascular disease

A team of scientists and doctors at UC Davis Health has identified a cellular link between diabetes and one of its major complications: narrowing of blood vessels, which increases the risk of several serious health problems, including diseases heart and stroke.

The authors hope that their work will lead to diabetes treatments -; beyond the monitoring of blood glucose and insulin therapy -; which targets the molecular source of its adverse effects on the vascular system.

The same team previously discovered that hyperglycemia, a symptom characteristic of diabetes, activates an enzyme called protein kinase A (PKA), which increases the activity of calcium channels and contracts blood vessels.

It was a surprise because the PKA is usually badociated with widening blood vessels and was not really on our radar. We wanted to understand the molecular processes that created this opposite reaction. "

Lead author Manuel Navedo, professor of pharmacology, UC Davis Health

For the new study published in the Journal of Clinical Investigation, the Navedo laboratory team conducted a series of experiments on the effects of high glucose levels on cerebral blood vessels and arterial cells that control blood flow. The tests were performed on mouse and two mouse models of genetically modified diabetes developed by UC Davis for cardiovascular health studies.

The researchers focused on the relationship between PKA and adenylyl cyclase (AC) -; an enzyme involved in the production of cyclic AMP (cAMP), a cellular messenger playing a vital role in the function of vascular cells. Their results showed that one AC in particular -; AC5 -; activation of cAMP and PKA mediated, triggering increased calcium channel activity and narrowing of blood vessels They also found that AC5 was essential for constricting blood vessels during diabetes.

The team now hopes to test the effects of the AC5 chain reaction under high glucose conditions in human cells. This step could confirm that there is a target treatment to reduce vascular complications of diabetes including ocular, renal, cerebral, gastrointestinal and cardiovascular diseases.

"We see every day in our clinics the devastating impact of diabetes on the health and lives of our patients," said co-author, Nipavan Chiamvimonvat, professor specializing in cardiovascular medicine at the University of California , UC Davis Health. "Our work highlights in a much clearer way how high blood glucose can damage the vascular system and gives us a new target to block its effects."