Serotonin modulates hepatic 6-phosphofructo-1-kinase in an insulin synergistic manner.
Human and rat hepatic tissue express many serotonin (5-HT) receptor subtypes, such as 5-HT(1B), 5-HT(2A), 5-HT(2B) and 5-HT(7) receptors, which mediate diverse effects. 5-HT is known to regulate several key aspects of liver biology including hepatic blood flow, innervations and wound healing. 5-HT is also known to enhance net glucose uptake during glucose infusion in fasted dogs, but little is known about the ability of 5-HT to control hepatic glucose metabolism, especially glycolysis. This study addresses the potential of 5-HT to regulate PFK activity and the mechanisms related to the enzyme activity. Based on our results, we are the first to provide evidence that 5-HT up-regulates PFK in mouse hepatic tissue. Activation of the enzyme occurs through the 5-HT(2A) receptor and phospholipase C (PLC), resulting in PFK intracellular redistribution and favoring PFK association to the cytoskeletal f-actin-enriched fractions. Interestingly, 5-HT and insulin act in a synergistic manner, likely because of the ability of insulin to increase fructose-2,6-bisphosphate because the presence of this PFK allosteric regulator enhances the 5-HT effect on the enzyme activity. Together, these data demonstrate the ability of 5-HT to control hepatic glycolysis and present clues about the mechanisms involved in these processes, which may be important in understanding the action of 5-HT during the hepatic wound healing process.
Laboratório de Enzimologia e Controle do Metabolismo (LabECoM), Departamento de Fármacos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Wagner Santos
WS
Coelho
Daniel
D
Da Silva
Mônica Mesquita
MM
Marinho-Carvalho
Mauro
M
Sola-Penna
D000818:Animals; D004357:Drug Synergism; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051379:Mice; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D007328:Insulin; D012701:Serotonin; D010732:Phosphofructokinase-1; C068652:1-phosphofructokinase