Effects of high glucose and insulin on the mRNA expressions of TGF-β1, and TIMP-1 of hepatic stellate cells in rat

Abstract

Objective To explore the mechanism of diabetic hepatic fibrosis by observing effects of high glucose and insulin on expressions of transforming growth factor beta 1 (TGF-β1) and tissue inhibitor of metalloproteinase (TIMP-1) mRNAs of hepatic stellate cell (HSC) in rat. Methods Hepatic stellate cell lines in vitro were administrated by different dose of glucose without insulin and glucose with insulin for 72 h, and mannitol was chosen as hyperosmosis control group. Real time fluorescent quantitation polymerase chain reaction (RT-FQ-PCR) was used to determine expressions of TGF-β1 and TIMP-1 mRNAs of HSC in each group. Results Expressions of TGF-β1 and TIMP-1 mRNAs of HSC in each group could be detected and showed no significant difference among groups (P>0.05). However, in general, expression of TGF-β1 mRNA in glucose with insulin group decreased and TIMP-1 mRNA increased. Conclusions The mRNA expressions of TGF-β1 and TIMP-1 in HSC could not be induced by high glucose alone, high dose of insulin may increase expressions of HSC TIMP-1 and reduce TGF-β1 expression. The main mechanisms of diabetic hepatic fibrosis may not be TGF-β1 pathway but be closely related to TIMP-1 pathway. Key words: Glucose/PD; Insulin/PD; Hepatocytes/ME; Transforming growth factor beta/ME; Tissue inhibitor of metalloproteinase-1/ME