Insulin, Insulin-Like Growth Factor I and Platelet-Derived Growth Factor Interact Additively in the Induction of the Protooncogenec-mycand Cellular Proliferation in Cultured Bovine Aortic Smooth Muscle Cells

Abstract

Vascular smooth muscle cell (SMC) growth is under the influence of various growth factors. We demonstrate that platelet-derived growth factor (PDGF) stimulates DNA synthesis of cultured bovine aortic SMCs by 2.5- to 3.5-fold. PDGF also exhibits additivity with insulin and insulin-like growth factor I (IGF-I) for DNA synthesis and cellular proliferation. Insulin (2 x 10(-6) M), IGF-I (1 x 10(-8) M), and PDGF (1 x 10(-9) M) cause a 60-80% increase in cell numbers over basal, but PDGF with insulin or IGF causes a 40-150% increase over basal. No additivity between insulin and IGF-I is evident. PDGF also induces commitment to DNA synthesis earlier than insulin or IGF-I. After exposure to PDGF for 4 h, SMCs incorporate 3H-thymidine to 60% of maximum (with PDGF alone) levels (achieved after exposure of 12 h or longer). Insulin and IGF-I exposure for 4 h, on the other hand, achieves 3H-thymidine incorporation that is only a 20-30% of maximum (with insulin or IGF-I alone). Insulin, IGF-I, and PDGF increase mRNA levels of the protooncogene c-myc. This induction begins within 30 min of exposure to these growth factors which causes a 4- to 6-fold increase in c-myc mRNA levels. Additivity is also observed between PDGF with insulin or IGF-I, but not between insulin or IGF-I, in c-myc induction. C-myc mRNA levels remain elevated as long as the hormones are present, although there's a tendency for the mRNA levels to fall off with insulin and IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-mediated "pseudoacromegaly"

“…42,43 In addition to its effects on cancer cell growth, hyperinsulinaemia may also stimulate the proliferation and migration of vascular smooth muscle cells via activation of the MAP kinase pathway. 44 This can lead to deleterious vascular effects.…”

Effect of an Insulin Sensitizer, Pioglitazone, on Hypertension in Fructose-Drinking Rats.

“…Hyperinsulinemia has been reported to enhance sodium ion reabsorption from the kidneys (9, 10), activate the sympathetic nervous system (11,12) or activate the sodium-proton pump and increase intracellular sodium and calcium ion (18), and proliferate the vascular smooth muscle cells (19,20). We have also found that the growth of smooth muscle cells from the explanted thoracic aorta in pioglitazone-treated WKY-F rats was lower than that in non-reated WKY-F rats (data not shown).…”

The Effect of Tumor Necrosis Factor-.ALPHA. on Tissue Specificity and Selectivity to Insulin Signaling

“…Recent studies have indicated that insulin resistance and compensatory hyperinsulinemia may cause high blood pressure due to factors such as prompted sodium reabsorption (2), proliferation of vascular smooth muscle cells (3), and stimulation of the sympathetic nervous system and the renin-angiotensin system (4,5). Imazu et al have indicated that hyperinsulinemia is an independent predictor of the development of hypertension (6).…”