Je. Friedman et al., GLUCOCORTICOIDS REGULATE THE INDUCTION OF PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP) GENE-TRANSCRIPTION DURING DIABETES, The Journal of biological chemistry, 268(17), 1993, pp. 2952-2957
The hormonal regulation of transcription of the phosphoenolpyruvate ca
rboxykinase (GTP) (4.1.1.32) (PEPCK) gene during diabetes was studied
using transgenic mice containing a chimeric gene consisting of segment
s of the PEPCK promoter (-2000/+73, -460/+73, -355/+73) linked to bovi
ne growth hormone (bGH) reporter gene. The effect of diabetes and insu
lin on transgenic mice containing a mutation in cAMP regulatory sequen
ces at -90/-82 and -250/-234 was also studied. In addition, we analyze
d the transcriptional response of the PEPCK gene to adrenalectomy, the
administration of glucocorticoids, and alterations in dietary protein
and carbohydrate. Our results indicate that deletion of the insulin r
egulatory sequence of the PEPCK promoter did not affect dietary contro
l of PEPCK gene expression. However, glucocorticoids and the glucocort
icoid regulatory unit appear to be essential for induction of PEPCK ge
ne transcription by diabetes. By contrast, mutation of cAMP regulatory
elements of the PEPCK promoter did not limit induction of PEPCK trans
cription by diabetes, nor did it affect negative regulation of transcr
iption by insulin. These results provide evidence for the interaction
of insulin and glucocorticoid regulatory elements in the control of PE
PCK gene transcription and suggest an important role of glucocorticoid
s as a gluconeogenic activator during diabetes.