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

Fertil Steril. 2006 Oct;86(4 Suppl):1217-22. doi: 10.1016/j.fertnstert.2006.04.022. Epub 2006 Sep 7.

Abstract

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.

MeSH terms

  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Glucose / administration & dosage
  • Glucose / pharmacology
  • Humans
  • Hyperglycemia / metabolism*
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Peritoneal Diseases / metabolism*
  • Peritoneal Diseases / pathology
  • Peritoneum / cytology
  • Peritoneum / metabolism*
  • RNA, Messenger / metabolism
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Adhesions / metabolism
  • Tissue Adhesions / pathology

Substances

  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Receptor, Insulin
  • Glucose