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

Abstract

ABSTRACT. The objective of this study was to investigate the mRNA expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) after gastric bypass surgery (GBS) in rats with type 2 diabetic mellitus (T2DM). Thirty-six male Goto-Kakizaki rats, aged 12 weeks, were randomly divided into the GBS, sham operation with diet restriction (SO), and sham operation alone (control) groups (N = 12 per group). Liver specimens from all rats were obtained during the operation and 8 weeks after operation. Blood lipid levels were measured before and 8 weeks after operation. Fasting blood glucose (FBG), food intake, and body weight were recorded at weekly time points after operation. The blood glucose area under the curve (AUC) was calculated, and insulin sensitivity indices (ISI) were assessed. The expression PEPCK mRNA and protein were measured by real-time polymerase chain reaction and western blot. Compared with those of the SO and control groups, the blood lipid levels and the FBG in the GBS group was significantly decreased (P < 0.05), as was the AUC (P < 0.05), whereas the ISI was significantly increased (P < 0.05). PEPCK mRNA and protein levels in the GBS group were lower than those in the control 16939 PEPCK expression after gastric bypass surgery in rats ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 16938-16947 (2015) group, whereas those in the SO group were significantly higher than those in controls (P < 0.05). In 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.

Combination Therapy with GABA and MgSO4 Improves Insulin Sensitivity in Type 2 Diabetic Rat

“…Hyperglycemia as one of diabetes pathogenesis is caused by several factors such as impaired insulin secretion, or PI3/AKT signaling [ 2 ], which leads to the impairment of the insulin-dependent glucose transporter 4 (Glut4) in muscles and hence the utilization of glucose decreases which is called peripheral insulin resistance [ 3 , 4 ]. Another important pathophysiology of diabetes is increasing glucagon secretion despite hyperglycemia [ 5 ]. In addition to lipolysis [ 6 ], the main target of glucagon is G protein-coupled receptors on the plasma membrane of hepatocytes [ 5 ] which finally upregulates phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6Pase), the key enzymes in gluconeogenesis, leading to an increase in hepatic glucose output; thus, an increase in gluconeogenesis is linked to the overexpression of PEPCK and G6Pase [ 5 ].…”

“…Another important pathophysiology of diabetes is increasing glucagon secretion despite hyperglycemia [ 5 ]. In addition to lipolysis [ 6 ], the main target of glucagon is G protein-coupled receptors on the plasma membrane of hepatocytes [ 5 ] which finally upregulates phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6Pase), the key enzymes in gluconeogenesis, leading to an increase in hepatic glucose output; thus, an increase in gluconeogenesis is linked to the overexpression of PEPCK and G6Pase [ 5 ].…”

“…Many antidiabetic drugs with different target receptors are being used in the clinic right now to decrease blood glucose [ 5 ]. Because type 2 diabetes mellitus (T2DM) is a complicated disease, patients are usually treated with a mixture of antidiabetic drugs.…”

“…Therefore, nowadays, multidrug therapies are reinvestigated; [ 8 ] it is believed that combination therapies with diverse mechanisms may also be a first-line choice [ 9 ]. Antidiabetic drugs mechanisms include reducing insulin resistance, diminishing hepatic glucose production, enhancing endogenous insulin secretion, and limiting glucose reabsorption [ 5 ].…”

Effect of gastric bypass combined with ileal transportation on type 2 diabetes mellitus

“…It has been reported that the expression of phosphoenolpyruvate carboxykinase (PEPCK) is upregulated in a rat model of diabetes and these rats are either completely lacking in insulin or exhibit increased plasma glucocorticoid levels (15,16). Glucose-6-phosphatase (G-6-Pase) is the final gatekeeper of glucose efflux from cells and catalyzes the last step of gluconeogenesis (17).…”