Control of gluconeogenesis: role of fatty acids in the alpha-adrenergic response.
Phenylephrine increases hepatic gluconeogenesis for as long as it is present in the extracellular medium. This effect is accompanied by a parallel increase in oxygen consumption. No apparent stoichiometric relationship exists between the phenylephrine-stimulated respiration and the energy required to meet the demands of gluconeogenesis. In the absence of extracellular calcium, no sustained stimulation of respiration was observed and phenylephrine failed to enhance gluconeogenesis; however, acute and transient effects of the alpha-adrenergic agonist were still observable. The following observations indicate that fatty acids are not involved in the alpha-adrenergic response: (1) the effects of phenylephrine and octanoate on respiration and gluconeogenesis were found to be additive; (2) unlike phenylephrine, octanoate is capable of stimulating gluconeogenesis in calcium-depleted liver; (3) in the absence of calcium, phenylephrine was incapable of further stimulating respiration or gluconeogenesis in the presence of octanoate. It is concluded that the conditions of increased lipid mobilization and/or oxidation are not sufficient to explain the metabolic response to alpha-adrenergic agonists. Fatty acids and alpha-adrenergic stimulation share a common role of stimulating gluconeogenesis in a manner dependent on their ability to stimulate respiration; however, the additive nature of their effects and distinct calcium requirements indicate that they act to trigger different mechanisms.
González-Manchón
C
C
Endocrine Physiology Unit, Centro de Investigaciones Biológicas, C.S.I.C., Madrid, Spain.
Sánchez-Ayuso
M
M
Parrilla
R
R
D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology*; D011773:Pyruvates / Q000378:metabolism / Q000494:pharmacology; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D002210:Caprylates; D007773:Lactates; D011773:Pyruvates; D010656:Phenylephrine; D019344:Lactic Acid; D019289:Pyruvic Acid; C031492:octanoic acid