PEPCK is an enzyme critical in the process of gluconeogenesis whose inhibition could be used to treat hyperglycemia and diabetes.
PEPCK catalyzes the first committed step in hepatic gluconeogenesis and is a key regulator of blood glucose homeostatis. Overexpression of this enzyme results in pre-diabetes and diabetes. PEPCK expression is stimulated by glucagon, glucocorticoids, retinoic acid and adenosine 3', 5'-monophosphate (cAMP) and is inhibited predominantly by insulin. Insulin levels of diabetic patients are insufficient to adequately inhibit PEPCK. Inhibition of PEPCK with siRNA led to complete elimination of hyperglycemia in a diabetic mouse model.