A new study shows a cellular connection between diabetes and
blood vessel narrowing that boosts one's risk of chronic and
potentially fatal health conditions, including stroke and heart
A team of researchers at the University of California has found
a link between diabetes and vascular disease, one of its major
The researchers hope that the findings of the study can help
formulate new treatments for diabetes, beyond just controlling and
monitoring blood glucose levels. The cellular level connection may
help new treatments target the molecular source of high blood
glucose's damaging effects on the blood vessels.
In the past, the team conducted a similar study, analyzing
hyperglycemia or high blood glucose and how it triggers an enzyme
known as protein kinase A (PKA), which in turn, boosts calcium
channel action, resulting in blood vessel constriction.
"This was a surprise since PKA is typically associated with
blood vessel widening and wasn't really on our radar. We wanted to
understand the molecular processes that created this opposite
reaction," Manuel Navedo, Professor of Pharmacology at UC Davis
But the mechanism by which glucose activates PKA remains
unclear, the researchers noted. In the study published in The
Journal of Clinical Investigation, they showed that elevating
extracellular glucose triggers cyclic adenosine monophosphate
(cAMP), the second messenger that's vital for biological processes
with a critical role in vascular cell function and production in
arterial myocytes, which was particularly dependent on adenylyl
cyclase 5 (AC5) activity.
The team performed experiments on the impact of elevated glucose
on arterial cells and cerebral blood vessels, which control and
maintain blood flow in the vessels. The researchers tested these on
laboratory mice, two mouse models of diabetes and a genetically
Specifically, they focused on the connection between PKA and
adenylyl cyclase (AC), an enzyme involved in cyclic AMP (cAMP)
production. They found that AC5 facilitated cAMP and PKA
activation, stimulating increased calcium channel activity and
subsequent blood vessel vasoconstriction. Also, they discovered
that AC5 was crucial for blood vessel vasoconstriction during
Vascular complications during diabetes are the main risk factors
for cardiovascular illnesses, such as hypertension, heart disease,
and stroke. These complications are often associated with increased
blood glucose levels or hyperglycaemia.
The team anticipates doing further tests on the impact of the
AC5 chain reaction in humans. The study may pave the way for new
treatment approaches that target the reduction of vascular
complications of diabetes.
The study on vascular effects of elevated blood glucose levels
at the cellular level could open the doors for new treatment
modalities to combat diabetes and cardiovascular diseases.
Syed, A., Reddy, G., Ghosh, D., Prada, M. P., Nystoriak, M.,
Morotti, S., Grandi, E., Sirish, P., Chaimvimonvat, N., Hell, J.,
Santana, L., Xiang, Y., Nieves-Cintron, M., and Navedo, M. (2019).
Adenylyl cyclase 5-generated cAMP controls cerebral vascular
reactivity during diabetic hyperglycemia. The Journal of Clinical