Effect of insulin and insulin-like growth factor-1 on vascular smooth muscle cells

Abstract

Non-insulin-dependent diabetes mellitus, obesity, and essential hypertension are associated with hyperinsulinemia that results from insulin resistance and insulin has been reported to accerelate atherosclerosis. We studied the effects of insulin and insulin-like growth factor-1 (IGF-1) on the growth of porcine vasucular smooth muscle cells and on the synthesis of extracellular matrix. The cells were cultured 3-8 changes of Dulbecco's modified Eagle's medium (DMEM) with 10% FCS. Subconfulent cells were put in wells 1 X 104 or 1 X 105 cells/well in DMEM with or without insulin or IGF- 1. The number of cells was counted, and protein and DNA synthesis, expression of genes for collagen α1 (1), and collagen synthesis were measured. Insulin (0, 16, and 160 nM) and IGF-1 (0, 1, 31, and 13.1 nM) increased number of cells by 50% and 40%, in a dose-dependent manner. Protein and DNA synthesis were also increased by insulin (3.8 and 3.0 times) and by IGF-1 (3.9 and 1.8 time). Collaged protein synthesis was increased 2.3-fold by IGF-1 at 13.1 nM, and insulin (16,000 nM) caused a 26.5-fold increase. Levels of collagen α1(1) mRNA were also increased by both insulin and IGF-1. These results suggest that insulin and IGF-1 can cause vascular hyperplasia associated with increased collagen synthesis, which indicates that insulin, IGF-1, or both may have an important role in vascular growth.