Insulin suppresses endothelial secretion of C-type natriuretic peptide, a novel endothelium-derived relaxing peptide.
We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells (ECs) and acts as an endothelium-derived relaxing peptide. We further demonstrated the detection of the gene transcripts of CNP and atrial natriuretic peptide (ANP) B receptor, a specific receptor for CNP, in human blood vessels. We thus propose the existence of a vascular natriuretic peptide system (NPS). CNP secretion was also demonstrated to be stimulated by various growth factors and cytokines. To clarify the significance of vascular NPS in proliferative vascular complications associated with diabetes, hypertension, or atherosclerosis, in the present study we examined the effect of insulin on CNP secretion from cultured ECs. Insulin at a concentration in the physiological range (10(-10)-10(-7) mol/l) potently suppressed CNP secretion, whereas insulin at the same concentration did not suppress endothelin (ET) secretion from EC. IGF-I had no significant effect on CNP secretion. Insulin, therefore, can be a potent inhibitor of CNP secretion through the activation of insulin receptor. Since CNP has been shown to be a potent inhibitor of vascular smooth muscle cell proliferation, the present study suggests the possibility that attenuated activity of vascular NPS is associated with hyperinsulinemia, which might result in proliferative vascular lesions.
Igaki
T
T
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
Itoh
H
H
Suga
S
S
Komatsu
Y
Y
Ogawa
Y
Y
Doi
K
K
Yoshimasa
T
T
Nakao
K
K
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type; D011506:Proteins / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects
D016232:Endothelins; D007328:Insulin; D011506:Proteins; D020098:Natriuretic Peptide, C-Type; D007334:Insulin-Like Growth Factor I