STRUCTURAL AND FUNCTIONAL-ANALYSIS OF THE HUMAN PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE PROMOTER

Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the rate limiting step in hepatic and renal gluconeogenesis. Glucagon (acting via cyclic AMP (cAMP)) and glucocorticoids stimulate PEPCK gene transcription, w hereas insulin has the opposite effect. Since these are the major regu latory hormones controlling glucose homeostasis, and because increased hepatic glucose production is one of the characteristics of non-insul in dependent diabetes mellitus (NIDDM), investigators have speculated that the regulation of PEPCK gene expression may be defective in patie nts with NIDDM. To begin to investigate this possibility we have isola ted and sequenced the human PEPCK gene promoter. In addition, we have constructed and analyzed a human PEPCK promoter-chloramphenicol acetyl transferase (CAT) fusion gene in an effort to correlate differences be tween the rat and human promoter sequences and the hormonal regulation of transcription.