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.


METHODS
Prospective experimental study.


METHODS
University medical center.


METHODS
Primary cultures of fibroblasts established from peritoneal and adhesion tissues of the same patients.


METHODS
Glucose treatment of the primary cultured fibroblasts for 24 hours with increasing concentrations of glucose (100-850 mg/dL).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Rizk
Natalie N
NN
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA. nrizk@med.wayne.edu
Saed
Ghassan M
GM
Diamond
Michael P
MP
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D010532:Peritoneal Diseases / Q000378:metabolism* / Q000473:pathology; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000267:Tissue Adhesions / Q000378:metabolism / Q000473:pathology
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D005947:Glucose