Ethanol-induced hyperlacticacidemia: inhibition of lactate utilization

Kreisberg, Robert A.; Owen, William C.; Siegal, Alan M.

doi:10.1172/jci106470

Cited by 95 publications

(27 citation statements)

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“…Lactic acidemia has been noted during alcohol intoxication in adults (24), and in the present study both maternal and fetal arterial lactate concentrations were increased, although the increase was most significant for the mother. Lactate could be used as an energy substrate during hypoglycemia or, alternatively, less of the glucose consumed could be used for lactate production.…”

Section: Discussionsupporting

confidence: 47%

Cerebral Responses to Acute Maternal Alcohol Intoxication in Immature Fetal Sheep

Gleason

Hotchkiss

1992

Pediatr Res

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ABSTRACT. Previous studies in mature fetal sheep have and behavioral problems (3). Several of these neurologic abnorshown that alcohol depresses cerebral blood flow (CBF), malities have been produced in animals exposed to alcohol in cerebral O2 consumption (CMR02), and cerebral glucose utero (4). However, the mechanism(s) by which alcohol produces consumption (CMRglu). This effect earlier in gestation brain damage and the vulnerable developmental period (if any) might contribute to the pathogenesis of fetal alcohol syn-during which damage occurs are unknown. The depressant efdrome. Physiologic studies of immature fetal sheep have fects of alcohol on CBF and CMR02 have been previously demonstrated lower CBF, CMR02, and CMRglu as well reported in several adult animal models as well as in mature fetal as a blunted vasodilatory response to hypoxia compared sheep. Richardson et al. (5) studied the physiologic responses of with mature fetal sheep. The purpose of this study was to term fetal sheep to acute maternal alcohol intoxication and noted determine whether immature fetal responses to alcohol are a significant decrease in both CBF and CMRO1. In addition, blunted compared with near-term fetal responses. We stud-they noted significant fetal hypoglycemia and a decrease in ied seven immature fetal sheep in utero at 92 f 1 d CMRglu. The fetal sheep brain is very mature near term, both gestation (term = 147 d) 2 d after placement of vascular structurally and functionally. Studies of immature fetal sheep catheters. Pure ethanol (1 g/kg) was infused i.v. to the have shown significantly lower CBF, CMR02, and CMRglu mother over 1 h. We measured CBF and myocardial blood compared with mature fetal sheep (6). Furthermore, the cerebral flow by radioactive microspheres and calculated CMROz vasodilatory response to hypoxemia is "blunted," reflecting either and CMRglu using arterial and sagittal sinus O2 and immature regulatory mechanisms or an inability of cerebral glucose concentrations. At a fetal ethanol concentration of vessels to respond to the usual stimuli (7). We theorized that 33 + 8 mmol/L (150 f 37 mg/dL), there were no significant cerebral responses to acute maternal alcohol intoxication may changes in CBF, CMR02, or CMRglu. There was mild be similarly blunted or absent in immature fetal sheep, and we hypoglycemia (glucose concentration = 1.05 f 0.2 versus therefore compared the physiologic responses to acute alcohol Subjects. Before initiating these studies, all surgical and experMild hypoglycemia and lactic acidemia did develop. The imental procedures were approved by the Animal Care and Use reason for the developmental differences in response to Committee at the University of California, San Francisco. Seven alcohol and their relationship to fetal alcohol syndrome mixed-breed fetal sheep were obtained from time-dated pregnanremain to be elucidated. (Pediatr Res 31: 645-648, 1992) cies.Surgiculpreparation. One d before surgery, food was withheld Abbreviations from the ewe, although she was allowed free access to ...

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Section: Discussionsupporting

confidence: 47%

Cerebral Responses to Acute Maternal Alcohol Intoxication in Immature Fetal Sheep

Gleason

Hotchkiss

1992

Pediatr Res

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“…As indicated by the failure of the recycled glucose specific activity to rise throughout the infusion period (panel C of Fig. 2 The combination of these results with previous observations that ethanol produced a prompt and sustained inhibition of lactate conversion to glucose (15) led us to design experiments in which glucose and lactate interconversion could be determined on the same day. Results of a representative study in which L-(+) lactate-U-14C and glucose-1-1'C were administered sequentially are shown in Fig.…”

Section: Resultsmentioning

confidence: 58%

“…Although such statements imply that ethanol only inhibits gluconeogenesis when substrate availability is limited, it is possible, as suggested recently (14), that inhibition of hepatic gluconeogenesis may occur in the nonfasted subject but be masked by the presence of adequate glycogen stores and concomitant glycogenolysis. Recent studies from this laboratory which demonstrated a prompt inhibitory effect of ethanol on lactate incorporation into glucose in the absence of hypoglycemia (15) support such a proposal.…”

mentioning

confidence: 89%

Glucose-lactate interrelationships: effect of ethanol

Kreisberg¹,

Siegal²,

Owen³

1971

J. Clin. Invest.

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A B S T R A C T The effect of ethanol on the interrelationship of lactate and glucose metabolism was investigated in eight human volunteers. Lactate and glucose kinetics and intervconversion rates were determined by the sequential administration of L-(+) lactate-U-14C and glucose-1-14C over an 8 hr period. After a 12 hr fast, the glucose turnover and recycling rates were 94.0 ±3.8 (SEM) and 13.7 ±1.1 mg/kg per hr, respectively. Approximately 50% of the glucose turnover or 40.7 ±2.1 mg/kg per hr was converted to lactate, accounting for 50% of the lactate turnover rate. Lactate turnover and lactate conversion to glucose were 81.8 ±6.2 and 16.7 ±1.1 mg/kg per hr, respectively. Approximately 20% of the glucose turnover was derived from lactate under these conditions. During the administration of ethanol, the blood lactate concentration doubled and the lactate turnover rate declined slightly. Lactate conversion to glucose was markedly inhibited, decreasing from 16 to 5 mg/kg per hr, and the per cent of the glucose turnover derived from lactate decreased from 18 to 6. Despite the marked inhibition of lactate conversion to glucose, neither the blood glucose concentration nor the glucose turnover rate changed. Both glucose recycling and glucose conversion to lactate were decreased, indicating that ethanol inhibited peripheral glucose utilization. There was no difference in the degree of inhibition of lactate incorporation into glucose produced by ethanol when nonfasted subjects were compared with two subjects who had fasted for 48-72 hr despite the presence of hypoglycemia in the latter.These results indicate that starvation is not a prerequisite for ethanol inhibition of gluconeogenesis from lactate in humans but is necessary for the development of hypoglycemia. Inhibition of lactate incorporation into glucose in nonfasted subjects is probably masked by a concomitant increase in glycogenolysis which prevents hypoglycemia. Ethanol decreases glucose conversion to lactate as well as lactate conversion to glucose, thus inhibiting the Cori cycle.

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“…Cette modification a des conséquences sur le cycle de Krebs [57], sur la glycolyse [54,58], sur la néoglucogenèse hépatique à partir des lactates [54,57,59,60] et sur la cétogenèse [61]. Les variations de lactatémie pourraient aussi être dues à des modifications [16,62,63], auxquelles l'acétate pourrait participer [64]. Mais l'influence du métabolisme de l'éthanol sur les concentrations sanguines des lactates est encore discutée.…”

Section: Discussionunclassified

Influence du site de prélèvement sur l’étude cinétique et métabolique de l’éthanol

et al. 2012

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Résumé -Objectif : L'analyste n'obtenant pas toujours les mêmes prélèvements sanguins, nous proposons d'étudier l'influence du site de prélèvement sanguin sur l'étude cinétique et métabolique de l'éthanol. Méthode : Sur un modèle animal, le rat mâle Sprague-Dawley âgé de 7 à 9 semaines, les cinétiques sanguines de l'éthanol, sériques de l'acétate et du lactate, artérielles et veineuses, sont déterminées respectivement par analyse de l'espace de tête en chromatographie en phase gazeuse et électrophorèse capillaire de zone. L'animal est cathétérisé soit au niveau d'une artère fémorale, soit au niveau d'une veine caudale. Résultats : Lors de la phase d'absorption, l'éthanolémie artérielle croît plus rapidement et plus intensément que l'éthanolémie veineuse ; après la phase de distribution, elles tendent à se confondre. Contemporainement, les acétates, métabolites de l'éthanol, apparaissent plus concentrés dans le compartiment artériel que veineux périphérique ; les lactates, produits indirects du métabolisme de l'éthanol, présentent une cinétique artérielle similaire à celle de l'acétate, les concentrations veineuses restant anormalement élevées pendant l'étude. Conclusion : Le sang veineux prélevé lors de cette étude n'a pas donné accès à la réalité cinétique et métabolique de l'éthanol. Ainsi, en comparaison avec le compartiment artériel, l'éthanol et l'acétate sont présents en quantité moindre dans le sang veineux, l'éthanol y apparaissant plus lentement. Le sang veineux prélevé s'est même avéré inadapté à l'étude cinétique des lactates. Cette étude confirme, si nécessaire, que les résultats et l'interprétation d'une analyse sont préconditionnés par le prélèvement lui-même, ce dernier n'étant pas toujours réalisé sous les indications d'un analyste. Mots clés :Recueil de prélèvements sanguins/méthode, éthanol/sang, éthanol/métabolisme, acétates/sang, lactates/sang Abstract -Objective: Because the analyst does not always obtain the same sampling of blood, we suggest studying the influence of the site of blood sampling on kinetic and metabolic studies of ethanol. Method: On an animal model, 7-to-9-week-old Sprague-Dawley male rats, arterial and venous blood kinetics of ethanol and serum kinetics of acetate and lactate were, respectively, determined by head-space chromatography analysis and capillary zone electrophoresis. The animal is catheterized either at the femoral artery, or at the caudal vein. Results: During the absorption phase, the arterial blood ethanol grew more quickly and more intensely than the venous; after the distribution phase, they tended to merge. At the same time, acetates, produced during ethanol metabolism, were more concentrated in the arterial compartment than the venous; lactates, indirect products of ethanol metabolism, presented an arterial kinetics similar to acetate, and venous concentrations remained abnormally high throughout the study. Conclusion: The venous blood samples taken during this study did not give access to the kinetic and metabolic reality of ethanol. So, compared with t...

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Ethanol-induced hyperlacticacidemia: inhibition of lactate utilization

Cited by 95 publications

References 27 publications

Cerebral Responses to Acute Maternal Alcohol Intoxication in Immature Fetal Sheep

Cerebral Responses to Acute Maternal Alcohol Intoxication in Immature Fetal Sheep

Glucose-lactate interrelationships: effect of ethanol

Influence du site de prélèvement sur l’étude cinétique et métabolique de l’éthanol

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