Hepatic Ketogenesis and Gluconeogenesis in Humans

Abstract

A B S T R A C T Splanchnic arterio-hepatic venous differences for a variety of substrates associated with carbohydrate and lipid metabolism were determined simultaneously with hepatic blood flow in five patients after 3 days of starvation.Despite the relative predominance of circulating Phydroxybutyrate, the splanchnic productions of both fhydroxybutyrate and acetoacetate were approximately equal, totaling 115 g/24 h. This rate of hepatic ketogenesis was as great as that noted previously after 5-6 wk of starvation. Since the degree of hyperketonemia was about threefold greater after 5-6 wk of starvation, it seems likely that the rate of ketone-body removal by peripheral tissues is as important in the development of the increased ketone-body concentrations observed after prolonged starvation as increased hepatic ketonebody production rate.

Splanchnic Uptake and Release of Energy Substrates in the Fasting Baboon Infant

“…Because hepatic vein catheterization has not proved technically feasible in this preparation, the following formula utilizing the Fick principle was employed to derive estimates of HV, based upon determinations of FLC, FSP, and substrate concentrations V2 and Vl. This formula cannot be validated in the neonatal baboon, but values for glucose production derived by this technique agree well with previous data for glucose turnover in the neonate and hepatic glucose production in adult humans (4,5,7,9,15). …”

“…In previous studies of renal glucose production using the same methodology, glucose production could also be related to arterial lactate (20). It may be noted that, although in adult man lactate normally accounts for less than 50% of total gluconeogenic equivalents taken up by the splanchnic bed (9), studies of the neonates of several species (29) would tend to substantiate the primacy of lactate as a gluconeogenic precursor in early life. As we have noted in studies of lactate release from peripheral tissues of the baboon neonate, glucose recycling through lactate is an active mechanism in this model and in the young of other species (2 1).…”

The Population Pharmacokinetics of d-β-hydroxybutyrate Following Administration of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate

“…R-1,3-butanediol is further metabolised in the liver and blood to produce BHB (14,15). BHB in the liver is metabolised to AcAc and acetone (16). BHB and AcAc in blood circulation are taken up by extra hepatic tissues and are used as energy source (17).…”

Interorgan Coordination of the Murine Adaptive Response to Fasting

“…When fasting is continued, muscle protein catabolism declines, and hepatic uptake of amino acids decreases, which is reflected in a decline of endogenous glucose production (6) and urinary nitrogen excretion (4,7). Lipid catabolism and the (hepatic) production of ketone bodies also increases rapidly and is quantitatively similar after 3 days and 5-6 weeks of starvation (8), but plasma levels increase only gradually to plateau after 4 weeks (4,9). The associated increase in urinary ketone body (organic-acid) excretion requires a compensatory increase in ammonia production and urinary excretion (4,7,10), which is met by an increased renal amino acid uptake and gluconeogenesis (5,6).…”