For the first time, researchers have identified how type 2 diabetes (T2D) affects lymphatic vessels — a finding that could lay the groundwork for new therapies to improve the lives of people with the condition, according to a study recently published in Cardiovascular Research.
The scientists, led by Joshua Scallan, PhD, of the University of Missouri, examined the lymphatic integrity of transgenic mice and developed a new assay that “quantifies the solute permeability of murine collecting lymphatic vessels,” since studying lymphatic vessel function in animals has been a challenge for researchers, because unlike blood vessels, lymph vessels are clear and appear almost invisible. They write, “When compared to age-matched wild-type (WT) controls, the permeability of collecting lymphatics from diabetic, leptin receptor-deficient (db/db) mice was elevated >130-fold. Augmenting nitric oxide (NO) production by suffusion of L-arginine rescued this defect. Using pharmacological tools and eNOS−/- mice, we found that NO increased WT lymphatic permeability, but reduced db/db lymphatic permeability. These conflicting actions of NO were reconciled by the finding that phosphodiesterase 3 (PDE3), normally inhibited by NO signaling, was active in db/db lymphatics and inhibition of this enzyme restored barrier function.”
“When an individual has type 2 diabetes, cells in the lymphatic vessels aren’t producing enough nitric oxide, which is essential to maintaining the integrity of their endothelial layer so that they function properly,” Scallan says. “We found that by giving the lymphatic vessels L-arginine, an amino acid commonly found in red meat, poultry, dairy products, and nutritional supplements, we were able to boost their nitric oxide production and restore their ability to act as a barrier.”
The authors conclude that they have identified the first lymphatic vascular defect in T2D, as the disease causes an enhanced permeability due to low NO bioavailability. “Further,” they continue, “this demonstrates that PDE3 inhibition is required to maintain lymphatic vessel integrity, and represents a viable therapeutic target for lymphatic endothelial dysfunction in metabolic disease.”
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