Human forearm metabolism during progressive starvation

Owen, Oliver E.; Reichard, George A.

doi:10.1172/jci106639

Cited by 170 publications

(97 citation statements)

References 40 publications

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“…The mean preinfusion IRI concentrations after overnight and 3-and at the end of the 2 h study period. The decreases in blood glucose observed in each subject after the 3 and 24 day NaAcAc infusions exceeded the methodological errors (15). Fig.…”

Section: Resultsmentioning

confidence: 53%

Rapid Intravenous Sodium Acetoacetate Infusion in Man METABOLIC AND KINETIC RESPONSES

Owen¹,

Reichard²,

Markus³

et al. 1973

J. Clin. Invest.

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A B S T R A C T The metabolic and kinetic responses to rapidly intravenously administered sodium acetoacetate (1.0 mmol/kg body wt) was studied after an overnight fast in 12 male and female adults weighing between 88 and 215% of average body weight. Blood was obtained before, during, and after the infusion for determination of circulating concentrations of immunoreactive insulin, glucose, acetoacetate, 9-hydroxybutyrate and free fatty acids. In three obese subjects the studies were repeated after 3 and 24 days of total starvation.After the overnight fast acetoacetate rose rapidly reaching a peak concentration at the end of the infusion; 9-hydroxybutyrate concentrations also increased rapidly and exceeded those of acetoacetate 10 min postinfusion. Total ketone body concentration at the end of the infusion period was comparable to that found after prolonged starvation. After the initial mixing period, acetoacetate, P-hydroxybutyrate and total ketone bodies rapidly declined in a parallel manner. There were no obvious differences between the subjects with regard to their blood concentrations of ketone bodies. The mean plasma free fatty acid concentration decreased significantly during the 20th to 90th min postinfusion period; for example the control concentration of 0.61 mmol/liter fell to 0.43 mmolAiter at 60 min. In the three obese subjects studied repeatedly, fasting plasma free fatty acids decreased with acetoacetate infusion from 0.92 to 0.46 mmol/liter after the 3 day fast and from 1.49 to 0.71 mmol/liter after the 24 day fast. Acetoacetate infusion caused no changes in blood glucose concentration after an overnight fast. However, in the three obese subjects restudied after 3-and 24-day fasts blood glucose decreased, respectively, from 3.49 to 3.22 mmol/ liter and from 4.07 to 3.49 mmol/liter. The mean serum insulin concentration in all subjects significantly increased from 21 to 46 /U/ml at the completion of the Received for publication 13 March 1973 (aid in revised form 11 June 1973. infusion and rapidly declined. In the three obese subjects restudied after 3-and 24-day fasts an approximate twofold increase of serum insulin was observed after each acetoacetate infusion.The mean fractional utilization rate of exogenously derived ketone bodies for all 12 subjects after an overnight fast was 2.9% min'. In the three obese subjects studied after an overnight, 3 and 24 day fast the mean fractional utilization rates were 2.1%, 1.5%, and 0.6% min', respectively. Ketone body volumes of distribution in the overnight fasted subjected varied from about 18% to 31% of body wt, suggesting that ketone nodies are not homogenously distributed in the body water. In the three obese subjects restudied after 3-and 24-day fasts volumes of distribution remained approximately constant. When total ketone body concentrations in the blood were below 2.0 mmol/liter, there was a linear relationship between ketone body utilization rates and ketone body concentrations; no correlation was found when blood concentrations were higher.

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Section: Resultsmentioning

confidence: 53%

Rapid Intravenous Sodium Acetoacetate Infusion in Man METABOLIC AND KINETIC RESPONSES

Owen¹,

Reichard²,

Markus³

et al. 1973

J. Clin. Invest.

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“…This suggests that the fasting hyperglycemia was due to a resetting of the glucose-insulin relationship rather than to increased gluconeogenesis. After a fast of 3 or more days, peripheral tissues of man, mainly muscle and adipose tissue, derive about 10% of their substrate requiremients from glucose oxidation (44). This amounts to approximately 10 g of glucose oxidized/day by peripheral tissues.…”

Section: Resultsmentioning

confidence: 99%

Metabolic Effects of Exogenous Glucocorticoids in Fasted Man

Owen¹,

Cahill²

1973

J. Clin. Invest.

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“…The availability of high arterial concentrations of free fatty acids resulted in their apparently preferential utilization as an oxidative substrate at 24 days of fasting [9]. Thus, the observation of the dependence of glucose uptake by the fetal sheep hindlimb upon arterial glucose concentration is valid for fetuses of well fed and acutely fasted ewes, but may not be true in chronic starvation.…”

Section: Discussionmentioning

confidence: 99%

Glucose/Oxygen Quotients across the Hindlimb of Fetal Lambs

et al. 1973

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ExtractGlucose/oxygen quotients were determined across the hindlimbs of seven fetuses, for a total of five studies in fetuses of fed ewes and five studies in fetuses of fasted ewes. The glucose/oxygen quotient was found to be a function of the fetal arterial glucose concentration in mM, [a], described by the equation: glucose/oxygen quotient = -0.047 + 1.46 [a]. The dependence of glucose uptake by the fetal hindlimb upon arterial glucose concentration is the first demonstration of the effect of substrate availability on the metabolism of a fetal organ. SpeculationThe demonstration of glucose/oxygen quotients of 1.0 or greater for fetal tissues at a time in gestation when the umbilical glucose/oxygen quotient is 0.4-0.5 suggests two possible explanations: (/) there may be substrate specificity for oxidative metabolism for each fetal organ, and (2) non-glucose substrates such as amino acids taken up by the umbilical circulation may be utilized by the fetal liver for gluconeogenesis.

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Human forearm metabolism during progressive starvation

Cited by 170 publications

References 40 publications

Rapid Intravenous Sodium Acetoacetate Infusion in Man METABOLIC AND KINETIC RESPONSES

Rapid Intravenous Sodium Acetoacetate Infusion in Man METABOLIC AND KINETIC RESPONSES

Metabolic Effects of Exogenous Glucocorticoids in Fasted Man

Glucose/Oxygen Quotients across the Hindlimb of Fetal Lambs

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