Effect of glycerol on gluconeogenesis in isolated rabbit kidney cortex tubules.
In renal tubules isolated from fed rabbits glycerol is not utilized as a glucose precursor, probably due to the rate-limiting transfer of reducing equivalents from cytosol to mitochondria. Pyruvate and glutamate stimulated an incorporation of [14C]glycerol to glucose by 50- and 10-fold, respectively, indicating that glycerol is utilized as a gluconeogenic substrate under these conditions. Glycerol at concentration of 1.5 mM resulted in an acceleration of both glucose formation and incorporation of [14C]pyruvate and [14C]glutamate into glucose by 2- and 9-fold, respectively, while it decreased the rates of these processes from lactate as a substrate. In the presence of fructose, glycerol decreased the ATP level, limiting the rate of fructose phosphorylation and glucose synthesis. As concluded from the 'cross-over' plots, the ratios of both 3-hydroxybutyrate/acetoacetate and glycerol 3-phosphate/dihydroxyacetone phosphate, as well as from experiments performed with methylene blue and acetoacetate, the stimulatory effect of glycerol on glucose formation from pyruvate and glutamate may result from an acceleration of fluxes through the first steps of gluconeogenesis as well as glyceraldehyde-3-phosphate dehydrogenase. As inhibition by glycerol of gluconeogenesis from lactate is probably due to a marked elevation of the cytosolic NADH/NAD+ ratio resulting in a decline of flux through lactate dehydrogenase.
D000090:Acetoacetates / Q000494:pharmacology; D000818:Animals; D005943:Gluconeogenesis; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005990:Glycerol / Q000494:pharmacology*; D005994:Glycerophosphates / Q000096:biosynthesis; D007657:Ketone Bodies / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D011817:Rabbits
D000090:Acetoacetates; D005971:Glutamates; D005994:Glycerophosphates; D007657:Ketone Bodies; D007773:Lactates; D011773:Pyruvates; D019344:Lactic Acid; D018698:Glutamic Acid; C016635:acetoacetic acid; D019289:Pyruvic Acid; C029620:alpha-glycerophosphoric acid; D005990:Glycerol; D008751:Methylene Blue