Increased levels of eNOS-linked O-GlcNAc were detected, and significant decreases in the levels of both Ser-1177-phosphorylated eNOS and phosphorylated Akt, the upstream mediator of eNOS phosphorylation, were observed.
By Proceedings of the National Academy of Sciences, [RxPG] Biljana Musicki et al. demonstrate that the glycosylation of endothelial nitric oxide synthase (eNOS) by the monosaccharide O-GlcNAc inhibits proper erectile function in rats with type 1 diabetes. The phosphorylation of eNOS at Ser-1177 is an important step in the promotion of tumescence.
The enzyme's activity is regulated by extracellular stimuli including electrical stimulation, shear stress, and VEGF signaling. Previous research has shown that hyperglycemia-induced O-GlcNAc modification inhibits eNOS activity in blood vessels, but the physiologic relevance of this modification in diabetic vascular tissues is unclear. Musicki et al. induced diabetes in rats and examined the penile tissues of the animals.
Increased levels of eNOS-linked O-GlcNAc were detected, and significant decreases in the levels of both Ser-1177-phosphorylated eNOS and phosphorylated Akt, the upstream mediator of eNOS phosphorylation, were observed. Although electrical stimulation increased blood flow in penile tissue of control and diabetic rats, an increase in activated eNOS in diabetic rats was not seen.
VEGF administration and shear stress were similarly ineffective in the diabetic animals, with rates of full erectile status decreased by 40%, magnitude of erectile response decreased by 30%, and tumescence rise time decreased by 70%
Publication:
"Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectile dysfunction" by Biljana Musicki, Melissa F. Kramer, Robyn E. Becker, and Arthur L. Burnett
On the web:Full Text at Proceedings of the National Academy of Sciences
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