thesis

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

Abstract

Polybrominated diphenyl ethers (PBDEs) are synthetic flame-retardant chemicals that enter the environment and mammalian body and may disrupt glucose metabolism. This study investigated the effect of PBDEs on a key gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK). Forty-eight male Wistar rats were gavaged 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 liver PEPCK enzyme activity was assayed. PBDEs significantly decreased PEPCK Vmax (mumol/min/g liver weight) at 3 days by 26%; this reduction persisted through 28 days. PBDEs also reduced total PEPCK activity (mumol/min/liver) by 18% (3 days) to 41% (28 days). Fasting plasma glucose levels remained unaffected by PBDE treatment. Findings demonstrate that PBDEs reduce hepatic PEPCK Vmax as early as three days of treatment; the implications for this reduction in glucose homeostasis remain to be determined

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