Decreased hepatic response to glucagon, adrenergic agonists, and cAMP in glycogenolysis, gluconeogenesis, and glycolysis in tumor-bearing rats.
The response to glucagon and adrenaline in cancer cachexia is poorly known. The aim of this study was to investigate the response to glucagon, adrenergic agonists (α and β) and cyclic adenosine monophosphate (cAMP) on glycogenolysis, gluconeogenesis, and glycolysis in liver perfusion of Walker-256 tumor-bearing rats with advanced cachexia. Liver ATP content was also investigated. Rats without tumor (healthy) were used as controls. Agonists α (phenylephrine) and β (isoproterenol) adrenergic, instead of adrenaline, and cAMP, the second messenger of glucagon and isoproterenol, were used in an attempt to identify mechanisms involved in the responses. Glucagon (1 nM) stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis in the liver of healthy and tumor-bearing rats, but their effects were lower in tumor-bearing rats. Isoproterenol (20 µM) stimulated glycogenolysis, gluconeogenesis, and glycolysis in healthy rats and had virtually no effect in tumor-bearing rats. cAMP (9 µM) also stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis in healthy rats but had practically no effect in tumor-bearing rats. Phenylephrine (2 µM) stimulated glycogenolysis and gluconeogenesis and inhibited glycolysis and these effects were also lower in tumor-bearing rats than in healthy. Liver ATP content was lower in tumor-bearing rats. In conclusion, tumor-bearing rats with advanced cachexia showed a decreased hepatic response to glucagon, adrenergic agonists (α and β), and cAMP in glycogenolysis, gluconeogenesis, and glycolysis, which may be due to a reduced rate of regulatory enzyme phosphorylation caused by the low ATP levels in the liver.
['Biazi|Giuliana R|GR|', 'Frasson|Isabele G|IG|', 'Miksza|Daniele R|DR|', 'de Morais|Hely|H|', 'de Fatima Silva|Flaviane|F|', 'Bertolini|Gisele L|GL|', 'de Souza|Helenir M|HM|0000-0003-1426-4069']
D000255:Adenosine Triphosphate D000322:Adrenergic Agonists D058646:Adrenergic alpha-1 Receptor Agonists D000318:Adrenergic beta-Agonists D000818:Animals D002100:Cachexia D000242:Cyclic AMP D005934:Glucagon D005943:Gluconeogenesis D050261:Glycogenolysis D006019:Glycolysis D007545:Isoproterenol D008099:Liver D008297:Male D009369:Neoplasms D010477:Perfusion D010656:Phenylephrine D051381:Rats D017208:Rats, Wistar
hepatic response cancer ATP glucose metabolism hormones