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/microg 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.