The expression of PEPCK is tightly regulated at the transcriptional level by various hormonal signals. For instance, glucagon and cortisol upregulate PEPCK expression during fasting by activating transcription factors such as cAMP response element-binding protein (CREB) and glucocorticoid receptors. Conversely, insulin downregulates PEPCK expression by inhibiting these transcription factors and promoting the action of forkhead box O1 (FOXO1), a transcriptional repressor.
