To investigate the effect of metformin on the PERK-eIF2a pathway in PGRN - induced insulin - resistant cell model. METHODS: The 3T3-L1 Insulin-resistance cell model was constructed by dexamethasone and PGRN. Metformin was used to act on the cell model to screen out the optimal concentration group for reducing PGRN,The experiment was divided into the normal control group, dexamethasone group, and PGRN group. 4-PBA and metformin were used to act respectively.Western Blot was used to detect the expression of insulin signaling factor and PERK-eIF2a signaling factor in each group.RESULTS: After the action of PGRN and dexamethasone, p-Akt decreased,p-IRS-1, p-PERK, p-eIF2α increased while after the treatment with 4-PBA and metformin, p-Akt increased, p-IRS-1, p-PERK, p-eIF2α decreased.(P<0.05). CONCLUSION: Metformin acts on the insulin resistance cell model induced by PGRN, and its effect on PERK-eIF2a pathway and insulin pathway factor is consistent with that of endoplasmic reticulum stress inhibitor 4-PBA.It is suggested that metformin may reverse PGRN-induced insulin resistance by activating AMPK to inhibit the phosphorylation of PERK-eIF2α, an endoplasmic reticulum stress pathway.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology