Insulin and insulin-like growth factor-I promotes angiotensinogen production and growth in vascular smooth muscle cells.
BACKGROUND
Circulating insulin and insulin-like growth factor-I (IGF-I) levels are increased in patients with hypertension and insulin resistance. Since both hormones are known to have cell growth-promoting effects, they may contribute to the progression of vascular hypertrophy in patients with insulin resistance. Insulin-mediated activation of the vascular renin-angiotensin system (RAS) stimulates growth in cultured rat vascular smooth muscle cells (VSMC).


OBJECTIVE
In order to evaluate the role of IGF-I-mediated activation of components of the tissue RAS, we examined the effect of IGF-I receptor stimulation on cell proliferation, and production of angiotensinogen in cultured VSMC.


METHODS
Aortic VSMC were derived from male Sprague-Dawley rats. IGF-I and insulin-mediated DNA synthesis were estimated by 3H-thymidine uptake (3H-TdR) with or without the angiotensin I converting enzyme inhibitor, captopril. Moreover, angiotensinogen released by the cells to the culture medium was determined by radioimmunoassay with or without the anti-IGF-I receptor antibody alphaIR3 or captopril.


RESULTS
Both IGF-I and insulin increased 3H-TdR uptake by cultured rat VSMC (P < 0.05). Captopril blocked IGF-I and insulin-mediated 3H-TdR uptake (-34.4 +/- 1.9% and -32.7 +/- 1.8%, P < 0.05, respectively). IGF-I increased the angiotensinogen level in the medium by 30.6 +/- 2.9% (P < 0.01). Insulin also stimulated angiotensinogen synthesis by 26.3 +/- 2.2% (P < 0.01). Captopril and alphaIR3 significantly suppressed angiotensinogen production stimulated by both IGF-I and insulin.


CONCLUSIONS
These results indicate that IGF-I as well as insulin stimulates angiotensinogen production and growth in VSMC. Thus, both hormones may independently play a role in progression of the vascular hypertrophy and atherosclerosis in patients with hypertension and insulin resistance through activation of the tissue RAS.
Kamide
K
K
Division of Endocrinology, Department of Veterans Affairs, Greater Los Angeles Health Care System, Sepulveda, California 91343, USA.
Hori
M T
MT
Zhu
J H
JH
Takagawa
Y
Y
Barrett
J D
JD
Eggena
P
P
Tuck
M L
ML
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000096:biosynthesis*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013936:Thymidine / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D000911:Antibodies, Monoclonal; D007328:Insulin; D000808:Angiotensinogen; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D013936:Thymidine