Kinetic analysis of short-term effects of alpha-agonists on gluconeogenesis in isolated rat hepatocytes.
Isolated hepatocytes from fasted rats were perifused with glycerol as gluconeogenic substrate. Stimulation of gluconeogenesis with phenylephrine (10(-5) M) as alpha-adrenergic agonist consisted of two distinct phases. The first phase was a transient stimulation of gluconeogenesis and was accompanied by transient changes in cytosolic and mitochondrial redox state; this phase was abolished by the transaminase inhibitor aminooxyacetate. The second phase was a stable stimulation of less magnitude, without change in redox state and insensitive to addition of aminooxyacetate. It is concluded that the first phase is due to a transient enhancement of flux through the malate/aspartate shuttle and that the stable phase is probably due to a stimulation of mitochondrial glycerol-3-phosphate dehydrogenase and glycerol kinase.
Leverve
X M
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Groen
A K
AK
Verhoeven
A J
AJ
Tager
J M
JM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D005943:Gluconeogenesis / Q000187:drug effects*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D000625:Aminooxyacetic Acid; D010656:Phenylephrine