Insulin and insulin-like growth factor-I promotes angiotensinogen production and growth in vascular smooth muscle cells.

Abstract

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.

STUDY DESIGN:

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.

• Authors: K Kamide, M T Hori, J H Zhu, Y Takagawa, J D Barrett, P Eggena, M L Tuck
• Journal: Journal of hypertension (J Hypertens) Vol. 18 Issue 8 Pg. 1051-6 (Aug 2000) ISSN: 0263-6352 [Print] Netherlands
• PMID: 10953996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Antibodies, Monoclonal
• Insulin
• Angiotensinogen
• Insulin-Like Growth Factor I
• Receptor, IGF Type 1
• Thymidine

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Angiotensinogen (biosynthesis)
• Animals
• Antibodies, Monoclonal (pharmacology)
• Cell Division (drug effects)
• Cells, Cultured
• Insulin (pharmacology)
• Insulin-Like Growth Factor I (pharmacology)
• Male
• Muscle Development
• Muscle, Smooth, Vascular (cytology, growth & development, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptor, IGF Type 1 (antagonists & inhibitors)
• Renin-Angiotensin System (drug effects, physiology)
• Thymidine (metabolism)