Effects of metformin on plasma concentrations of glucose and mannose, G6Pase and PEPCK activity, and mRNA expression in the liver and kidney of chickens

Abstract

1. The objective of this study was to determine the effects of the gluconeogenesis inhibitor metformin on 21-d old chickens. The following parameters were measured in the liver and kidney: plasma glucose, plasma mannose, enzyme activities and mRNA expression levels of glucose-6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK). 2. Chickens were divided into two groups, and received either metformin (300 mg/kg body weight) or water. Plasma glucose and mannose concentrations were analysed by high performance liquid chromatography (HPLC). G6Pase and PEPCK activities were determined by glucose 6-phosphate and malic acid substrate methods, respectively. The expression levels of mRNA were determined by real-time PCR. 3. Plasma glucose and mannose reached their lowest concentrations 1 h after metformin administration. At 0·5 h-1 h after metformin administration, the enzyme activities and mRNA expression levels of G6Pase and PEPCK reached their lowest point in the kidney and their highest point in the liver. The decrease observed in the kidney may have been associated with reductions in both plasma glucose and mannose concentrations. 4. In conclusion, the effect of metformin on the kidney of chickens is similar to its effect in mammals. In contrast, no suppression of enzyme activity or mRNA expression was observed in chicken liver. Therefore, the mode of action of metformin, via AMPK activation, may be different in the chicken liver.

Accumulation of methylglyoxal and d‐lactate in Pb‐induced nephrotoxicity in rats

“…Metformin activated the AMP-activated protein kinase and provided pleiotropic beneficial effects (Zhou et al, 2001;Takiar et al, 2011). The activation of AMP-activated protein kinase would decrease phosphoenolpyruvate carboxykinase and glucose 6-phosphatase activity, which would mediate the gluconeogenesis (Sato et al, 2011;Aatsinki et al, 2014).…”

Regulation of a truncated isoform of AMP-activated protein kinase α (AMPKα) in response to hypoxia in the muscle of Pacific oyster Crassostrea gigas

“…Crassostrea gigas inhabits the intertidal zone and shows high tolerance to stress conditions such as hypoxia and heat shock (Kawabe and Yokoyama 2011a, b). In C. gigas, the adductor muscle is one of the primary organs involved in responses to biotic or abiotic environmental variations, such as hypoxia (Le Moullac et al 2007a;Samain and McCombie 2008). Valve closure is usually considered as a general stress response of marine bivalves to a wide variety of environmental stressors (Manley 1983;Akberali and Trueman 1985).…”

“…Activated AMPK can rapidly phosphorylate and activate a wide array of target key metabolic enzymes (Hardie 2004). Long-term effects of AMPK activity have also been demonstrated on the gene expression of several metabolic enzymes involved in glucose homeostasis (Viollet et al 2003;Hardie 2003;Sato et al 2011). Another signaling pathway linked to mammalian cell survival during energy deficiency in hypoxic conditions is the phosphatidyl inositol 3-kinases (PI3K)/protein kinase B (AKT) pathway, which regulates glucose metabolism and controls cell apoptosis (Kim et al 2012;Parcellier et al 2008;Alvarez-Tejado et al 2001).…”

Insulin Promotes the Expression of the Gluconeogenic Rate-Limiting Enzymes Phosphoenolpyruvate Carboxykinase (Pepck) and Glucose 6-Phosphatase (G6pase) through PI3k/Akt/mTOR Signaling Pathway in Goose Hepatocytes

“…Phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) are enzymes that limit gluconeogenesis rate (Sato et al, 2011). In addition, G6Pase is a critical enzyme in the last step of the glycogenolytic pathway (Podolin et al, 1999).…”