Yx. Ding et al., Effects of simulated hyperglycemia, insulin, and glucagon on endothelial nitric oxide synthase expression, AM J P-ENDO, 279(1), 2000, pp. E11-E17
Citations number
63
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Diabetes is associated with endothelial dysfunction and increased risk of h
ypertension, cardiovascular disease, and renal complications. Earlier studi
es have revealed that hyperglycemia impairs nitric oxide (NO) production an
d diabetes causes endothelial dysfunction in humans and experimental animal
s. This study was designed to test the effects of altered concentrations of
glucose, insulin, and glucagon, the principal variables in types I and II
diabetes, on NO production and endothelial NO synthase (eNOS) expression in
cultured human coronary endothelial cells. Cultured endothelial cells were
incubated in the presence of glucose at either normal (5.6 mM) or high (25
mM) concentrations for 7 days. The rates of basal and bradykinin-stimulate
d NO production (nitrate + nitrite) and eNOS protein expression (Western bl
ot) were then determined at the basal condition and in the presence of insu
lin (10(-8) and 10(-7) M), glucagon (10(-8) and 10(-7) M), or both. Incubat
ion with a high-glucose concentration for 7 days significantly downregulate
d, whereas insulin significantly upregulated, basal and bradykinin-stimulat
ed NO production and eNOS expression in cultured endothelial cells. The sti
mulatory action of insulin was mitigated by high-glucose concentration and
abolished by cotreatment of cells with glucagon. Thus hyperglycemia, insuli
nopenia, and hyperglucagonemia, which frequently coexist in diabetes, can w
ork in concert to suppress NO production by human coronary artery endotheli
al cells.