Hepatic phosphoenolpyruvate carboxykinase expression after gastric bypass surgery in rats with type 2 diabetes mellitus

Abstract

Objective To investigate mRNA expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) after gastric bypass surgery (GBS) in rats with type 2 diabetes mellitus (T2DM) . Methods 36 male Goto-Kakizaki rats, aged 12 weeks, were randomly divided into GBS, sham operation with diet restriction (SO) , and sham operation alone (control) groups (n=12 per group) . The blood lipid levels and fasting plasma glucose (FPG) levels in rats before and 8 weeks after surgery were measured and compared. The insulin sensitivity index (ISI) was calculated. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of PEPCK mRNA and protein in hepatocytes at 8 weeks after operation. Results 8 weeks after operation, the blood lipid levels [TC (1.25±0.08) mmol/L, TG (0.93±0.10) mmol/L, FFA (0.88±0.12) mmol/L] in GBS group were significantly lower than those before operation [TC (2.31±0.52) mmol/L, TG (1.44±0.27) mmol/L,FFA (1.08±0.06) mmol/L] (P<0.05) .The fasting blood glucose levels in GBS decreased from (11.73±0.37) mmol/L to (5.13±0.22) mmol/L (P<0.05) , and ISI in GBS group increased from (-5.78±0.10) to (-4.64±0.15) (P<0.05) . PEPCKmRNA (3.97±0.30) and protein (1.60±0.31) expression significantly reduced (P<0.05) . Conclusion GBS can reduce blood glucose in T2DM rats while improving glucose tolerance and hyperglycemia, and the mechanism appears to be associated with a decrease of hepatic PEPCK mRNA and protein expression. Key words: Gastric bypass surgery; Type 2 diabetes mellitus; Phosphoenolpyruvatecarboxykinase; Gluconeogenesis