Insulin is required for angiotensin II-mediated hypertrophy of smooth muscle cells.
The prevalence of hypertension and atherosclerosis among subjects with hyperinsulinemia supports the premise of a direct metabolic link between insulin and angiotensin II at the cellular level. In the present study, the effect of insulin on the angiotensin II-induced growth of A10 smooth muscle cells (SMC) was investigated. Treatment of quiescent A10 cells with angiotensin II caused an increase in RNA synthesis, proto-oncogene c-fos mRNA levels and cell size dependent upon pretreatment with insulin. The insulin requirement was independent of its actions as a growth factor, since a pre-treatment of at least 24 h with insulin was essential for growth stimulation by angiotensin II. Using RT-PCR, insulin was shown to regulate AT2 receptor expression in both quiescent and differentiating cells. These data suggest the AT2 receptor, which mediates the growth effects of angiotensin II in A10 cells, may be the critical target for the effect of insulin.
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
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Saward
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Zahradka
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D004347:Drug Interactions; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D007328:Insulin; D016760:Proto-Oncogene Proteins c-fos; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012313:RNA