The effect of in vivo PBDE treatment on hepatic phosphoenolpyruvate carboxykinase (PEPCK) enzyme kinetics in male wistar rats

Abstract

Xenobiotics such as phenobarbital, TCDD and PCB significantly suppress on the activity of a key gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), suggesting that xenobiotics could disrupt glucose metabolism. The effect of polybrominated diphenyl ethers (PBDEs), a family of synthetic flame‐retardant chemicals, on PEPCK is unknown. This study investigated the effect of PBDE treatment on PEPCK. Forty‐eight, one month‐old, male Wistar rats were gavaged daily with corn oil or corn oil containing 14 mg/kg DE‐71 for 3, 14 or 28 days (N = 8 per group). At each time point, fasting plasma glucose, insulin and C‐peptide were measured and hepatic PEPCK and CYP enzyme activities were assayed. PBDE treatment significantly decreased PEPCK Vmax (μmol/min/g liver weight) by 22% (3 days) to 44% (28 days). CYP1A, −2B and −3A Vmax were increased by 6‐, 6‐ and 30‐fold, respectively, in treated rats compared to control. There was a significant inverse and temporal correlation (r = −0.74) between CYP3A and PEPCK Vmax for the treatment group. Fasting plasma glucose, insulin and C‐pep levels were unaffected by treatment, but the glucose:insulin ratio tended (P=0.07) to be higher in treated compared to control rats. These data suggest that 3 days of in vivo PBDE treatment is sufficient to compromise liver glucose metabolism and 28 days of treatment may influence insulin sensitivity. Supported by NH Agr. Exp. Stn. grant #NH00541.