The effects of metformin on Pdx-1 and insulin gene expression in mouse embryonic and neonatal pancreas

Metformin is an oral anti-diabetic medication used to treat type 2 diabetes. Metformin treatment increases levels of active GLP-1. Activation of GLP-1 receptor signaling leads to enhanced expression of Pdx-1 mRNA transcripts in β-cell lines. The Pdx-1 gene is critical for β-cell differentiation and expression of the insulin gene. This study investigated the effect of metformin on Pdx-1 and insulin gene expression in mouse embryos and neonates. Pregnant C57BL/6 mice were randomly divided into two groups. The control group received normal saline, and the experimental group received 75, 150, or 250 mg/kg metformin by intraperitoneal injection once daily for 11 days. Half of the pregnant mice were then sacrificed by cervical dislocation on day 19.5 of pregnancy, and the pancreases of the embryos were dissected. The other half of the pregnant mice delivered their pups, and the pancreases of the neonatal mice were removed for assessment of Pdx-1 and insulin gene expression. The various doses of metformin did not change the expression of Pdx-1 or the insulin gene in the neonatal or embryonic experimental groups compared to the control groups (P > 0.05). Neonates from the metformin-treated groups showed a significant increase in expression of Pdx-1 and insulin compared to embryos from the metformin-treated groups (P < 0.05). The results indicate that metformin affects the regulatory region of the insulin gene after birth. The insensitivity of embryonic pancreases to metformin is probably due to their lack of functional maturity