Epigallocatechin gallate improves insulin sensitivity in rats experiencing catch-up growth after being small for gestational age by upregulating PDX1 expression.

BACKGROUND: Increasingly small for gestational age (SGA) newborns is an issue all over the world. In the early life of SGA, catch-up growth (CUG) may appear with elevated insulin resistance risk. Epigallocatechin gallate (EGCG) preserves therapeutic potential in metabolic disorders, however, the mechanism of EGCG's protective effects remains largely unclear. Our purpose is to investigate EGCG on insulin sensitivity during CUG in rats recovered from being SGA and to explore the potential underlying mechanism.

METHODS: We established a food restriction-based SGA rat model and selected CUG rats for EGCG treatment. Hyperinsulinemic-euglycemic clamp technique was used to measure glucose and insulin sensitivity. Furthermore, we assessed the apoptosis of islet pancreatic cells through TdT-mediated dUTP Nick-End Labeling (TUNEL) assays. Subsequently analyzed pancreatic PDX1 and proliferation-related protein PCNA, CDK4 and cyclin D2 expression by Western blot. Finally, we established a high glucose (HG)-induced insulin resistance MIN6 pancreatic β cell model. PDX1 knockdown was used to determine whether EGCG protect pancreatic β cell from HG damage by regulating PDX1 expression.

RESULTS: We found that EGCG treatment significantly ameliorated CUG rats exhibiting insulin resistance by regulating pancreatic cell apoptosis and proliferation. PDX1 expression was significantly decreased with pancreas damage in CUG rats, while EGCG upregulates PDX1 expression correlated with improved insulin sensitivity in pancreatic tissues. In vitro assays further validated PDX1 is downregulated in HG induced pancreatic β cell insulin resistance model, while EGCG promoted β cell survival rate and inhibited apoptosis by regulating PDX1 expression.

CONCLUSIONS: EGCG may enhance insulin sensitivity in CUG rats by upregulating pancreatic PDX1 expression.