[Effects of insulin-like growth factor-1 and insulin on modulating glucose metabolism and functions of lung fibroblasts].
OBJECTIVE
It is recognized that lung fibroblasts (LF) act as a common pathway in the development of fibrosis from alveolitis of whatever etiology. The study was undertaken to identify the modulating effects of insulin-like growth factor-1 (IGF-1) on LF glucose metabolism and functions, to explore possible therapeutic targets through modulating LF for the treatment of pulmonary fibrosis.


METHODS
Human embryonic lung (HEL) diploid fibroblast cells were cultured for 24 h with blank control, 100 ng/ml IGF-1, 200 ng/ml IGF-1, 100 ng/ml IGF-1 + 100 ng/ml insulin, 100 ng/ml IGF-1 + 200 ng/ml insulin, 100ng/ml insulin, 200 ng/ml insulin, respectively. The culture supernatants and cell pellets were collected to extract proteins and mRNAs. After quantitated with ultraviolet spectrometer, RT-PCR and Northern blotting were performed to determine the content of glucose transporter-4 (Glut-4), hexokinase II, elastin and collagen-IV.


RESULTS
RT-PCR showed that the general mean absorbance ratios of Glut-4 and HK-IImRNA in IGF-1 group were (0.67 +/- 0.25) and (0.60 +/- 0.19), significantly increased as compared with that of control group [(0.61 +/- 0.12), (0.55 +/- 0.19)]; but decreased as compared with that of insulin group [(0.74 +/- 0.26), (0.71 +/- 0.23)]. The expression of elastin, collagen protein in IGF-1 group [(174.3 +/- 4.2), (142.1 +/- 1.0)] were significantly stronger than that of insulin group.


CONCLUSIONS
IGF-1 can stimulate LF glucose metabolism, companied with increased expression of elastin and collagen IV in a concentration-dependent manner. IGF-1 can decrease the effect of insulin on LF glucose metabolism, whereas insulin can attenuate the effect of IGF-1 on LF in elastin and collagen expression.
Qin
Yong-xin
YX
Department of Infection Disease, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
Wan
Xian-yao
XY
Chen
Bai-yi
BY
D015152:Blotting, Northern; D002478:Cells, Cultured; D024142:Collagen Type VI / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000196:embryology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013056:Spectrophotometry, Ultraviolet
D024142:Collagen Type VI; D051275:Glucose Transporter Type 4; D007328:Insulin; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D004549:Elastin; D005947:Glucose