Effects of hyperglycemia on the differential expression of insulin and insulin-like growth factor-I receptors in human normal peritoneal and adhesion fibroblasts

Objective: To determine whether the insulin receptor (IR), insulin-like growth factor-I receptor (IGF-IR), and IGF-I are expressed differentially in fibroblasts isolated from normal peritoneal and adhesion tissue before and after 24-hour treatment with increasing glucose concentrations. Design: Prospective experimental study. Setting: University medical center. Patient(s): Primary cultures of fibroblasts established from peritoneal and adhesion tissues of the same patients. Intervention(s): Glucose treatment of the primary cultured fibroblasts for 24 hours with increasing concentrations of glucose (100-850 mg/dL). Main Outcome Measure(s): Real-time polymerase chain reaction was used to measure messenger RNA (mRNA) levels for IR, IGF-IR, and IGF-I. Enzyme-linked immunosorbent assay was used to determine protein levels. Result(s): At the normal glycemic level (100 mg/dL), adhesion fibroblasts have significantly higher mRNA levels of the IR (7.96 ± 0.15 vs. 6.97 ± 0.16; P<.05), IGF-IR (7.72 ± 0.22 vs. 6.88 ± 0.06; P<.05), and IGF-I (7.04 ± 0.10 vs. 5.92 ± 0.10; P<.05) when compared with normal fibroblasts, respectively. Data are expressed as log(mRNA/μg RNA). Normal fibroblasts respond to increasing glucose concentrations by increasing the expression levels of the IR, IGF-IR, and IGF-I, whereas adhesion fibroblasts respond by decreasing the expression of the IR, IGF-IR, and IGF-I. Conclusion(s): The differential expression of the IR, IGF-IR, and IGF-I in adhesion fibroblasts may contribute to the pathogenesis of fibrosis observed in diabetic patients.