Changes in liver gluconeogenesis during the development of Walker‐256 tumour in rats

Abstract

Few studies have investigated liver gluconeogenesis in cancer and there is no agreement as to whether the activity of this pathway is increased or decreased in this disease. The aim of this study was to evaluate gluconeogenesis from alanine, pyruvate and glycerol, and related metabolic parameters in perfused liver from Walker-256 tumour-bearing rats on days 5 (WK5 group), 8 (WK8 group) and 12 (WK12 group) of tumour development. There was reduction (P < 0.05) of liver glucose production from alanine and pyruvate in WK5, WK8 and WK12 groups, which was accompanied by a decrease (P < 0.05) in oxygen consumption. Moreover, there was higher (P < 0.05) pyruvate and lactate production from alanine in the WK5 group and a marked reduction (P < 0.05) of pyruvate and urea production from alanine in the WK12 group. In addition, liver glucose production and oxygen consumption from glycerol were not reduced in WK5, WK8 and WK12 groups. Thus the, the results show inhibition of hepatic gluconeogenesis from alanine and pyruvate, but not from glycerol, on days 5, 8 and 12 of Walker-256 tumour development, which can be attributed to the metabolic step in which the substrate enters the gluconeogenic pathway.

Celecoxib and Ibuprofen Restore the ATP Content and the Gluconeogenesis Activity in the Liver of Walker-256 Tumor-Bearing Rats

“…The reduced hepatic production of pyruvate, lactate and urea from alanine observed in tumor-bearing rats (Fig. 2) confirms our previous findings [6] and can be due to an inhibition of alanine aminotransferase, as suggested by others [31,32].…”

“…4) in the liver of tumor-bearing rats shows that these NSAIDs improve other steps of the gluconeogenesis pathway besides that catalyzed by alanine aminotransferase. The inhibition of glucose production from pyruvate and lactate, but not from glutamine [7] and glycerol [6], in tumor-bearing rats shows that this inhibition occurs at steps preceding the entry of glutamine and glycerol into the gluconeogenic pathway, such as the conversion of pyruvate to oxalacetate, a mitochondrial step catalyzed by pyruvate carboxylase, which is ATP dependent. In fact, a reduction in ATP content decreases the rate of gluconeogenesis by inhibiting pyruvate carboxylase [33].…”

“…To assess the gluconeogenesis, Walker-256 tumor-bearing rats were weighed, anesthetized with sodium pentobarbital (40 mg/kg) and subjected to in situ liver perfusion as previously described [6,20,21]. The perfusion fluid, Krebs-Henseleit buffer (KHB: 115 mM NaCl, 26 mM NaHCO 3 , 5.8 mM KCl, 1.2 mM Na 2 SO 4 , 1.18 mM MgCl 2 , 1.2 mM NaH 2 PO 4 and 2.5 mM CaCl 2 , pH 7.4), at 37ºC, and saturated with a 95%:5% O 2 :CO 2 mixture, was introduced into the liver (4 mL/min per gram of liver) through a cannula inserted into the portal vein, while a second cannula in the inferior vena cava was used to collect the effluent perfusate at 2 min intervals, to assess the production of glucose [22], lactate [23], pyruvate [24] and urea [25].…”

Hepatic Activation of the FAM3C-HSF1-CaM Pathway Attenuates Hyperglycemia of Obese Diabetic Mice

“…It had been believed that dysregulated glucose metabolism is involved in various cancers. Gluconeogenesis is reduced in rat liver with Walker-256 tumor (45). Dexamethasone attenuates hepatocellular carcinoma in mice with restored gluconeogenesis in malignant hepatocytes (46).…”

Contrast enhanced ultrasonography (CEUS) in the characterization of tumor microcirculation. Validation of the procedure in the animal experimental model

“…The rat Walker 256 tumor bears the name of it's discoverer, Prof. G Walker who identified it in 1928, as a spontaneous breast tumor in the pregnant albino rat [17]. Since then the tumor has been used in many model experiments on rats [18,19].…”