Alcohol Hypoglycemia. I. Carbohydrate Metabolism of Patients With Clinical Alcohol Hypoglycemia and the Experimental Reproduction of the Syndrome With Pure Ethanol*

Freinkel, Norbert; Singer, David; Arky, Ronald A.; Bleicher, Sheldon J.; Anderson, John B.; Silbert, Cynthia K.

doi:10.1172/jci104797

Cited by 206 publications

(45 citation statements)

References 56 publications

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“…Freinkel et al 2 were among the first investigators to report that acute doses of ethanol (hereafter, and perhaps inappropriately, referred to as "alcohol") can result in a significant decline in blood glucose levels. Further studies by Krebs and coworkers 3,4 determined that the oxidation of ethanol within the liver through the nicotinamide adenine dinucleotide (NAD + )-dependent alcohol dehydrogenase (ADH) pathway generates an elevation of cytosolic NADH, thereby increasing the NADH/NAD + ratio.…”

Section: Consumption On Glucose Homeostasismentioning

confidence: 99%

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

Sumida

Hill

Matveyenko³

2007

Clinical Medicine & Research

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Alcohol-induced hypoglycemia has traditionally been attributed to the amount of ethanol consumed rather than any inherent decline in glucose output capacity by the gluconeogenic organs and/or an increase in skeletal muscle glucose uptake. Further, while the potential for sex differences that might impact glucose homeostasis following chronic alcohol consumption has been recognized, direct evidence has been noticeably absent. This paper will provide a brief review of past and present reports of the potential for sex differences in glucose homeostasis following chronic ethanol consumption. This paper will also provide direct evidence from our laboratory demonstrating sex differences from chronic alcohol consumption resulting in a decrement in glucose appearance and more importantly, a specific decline in hepatic gluconeogenic (HGN) capacity in the absence and presence of ethanol. All our studies involved 8 weeks of chronic alcohol consumption in male and female Wistar rats, as well as a 24 to 48 hour fast to deplete hepatic glycogen stores. Under the conditions of chronic alcohol consumption and an acute dose of ethanol, we provide in vivo evidence of an early decline in whole body glucose appearance in females fed an ethanol diet compared to controls.While the decline was also observed in males fed the alcohol diet, it occurred much later compared to ethanol fed females. The site for the decline in whole body glucose production (i.e., either the kidneys or the liver) was beyond the scope of our prior in vivo study. In a follow-up study using the in situ perfused liver preparation, we provide additional evidence for a specific reduction in HGN capacity from lactate in ethanol fed females compared to ethanol fed males in the absence of alcohol in the perfusion medium. Finally, employing the isolated hepatocyte technique, we report decrements in HGN from lactate in ethanol fed females compared to ethanol fed males in the presence of ethanol in the incubation medium.The mechanism for the specific decline in HGN within the liver of ethanol fed females remains to be determined.To the extent that our observations in animals can be extrapolated to humans, we conclude that alcoholic women are more susceptible to ethanol-induced hypoglycemia compared to alcoholic men.

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Section: Consumption On Glucose Homeostasismentioning

confidence: 99%

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

Sumida

Hill

Matveyenko³

2007

Clinical Medicine & Research

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“…[1-13 C]Oleic acid, sodium [U- 13 C]acetate, sodium [1-13 C]acetate, [U- 13 C]citric acid, [1,[5][6][7][8][9][10][11][12][13] C]citric acid, and [U- 13 C] malonic acid were purchased from Isotec (Miamisburg, OH). [U- 13 C]malonyl-CoA was prepared from [U- 13 C]malonic acid as described previously [11], and purified by high pressure liquid chromatography.…”

Section: Experimental Procedures Materialsmentioning

confidence: 99%

“…The 13 C-labeling of the acetyl moiety of citrate (a probe of mitochondrial acetyl-CoA) was assayed by cleaving citrate with ATP-citrate lyase isolated from rat liver [18] and analyzing acetyl-CoA by ion trap liquid chromatography-mass spectrometry (LC-MS) [19]. The assay was set up using standards of [1,[5][6][7][8][9][10][11][12][13] C]citrate and [U- 13 C]citrate which generate M1 and M2 acetyl-CoA, respectively. In the calculations of molar percent enrichments (MPE) all raw data were corrected for natural abundance of 13 C.…”

Section: Analytical Proceduresmentioning

confidence: 99%

“…Adverse effects of acetate include hypoxemia and cardiovascular effects which have been ascribed to uncontrolled AMP degradation to adenosine [6]. In normal human volunteers, ingestion of ethanol results in a major decrease in whole-body lipid oxidation [7], and, in some cases to alcoholic hypoglycemia [8]. It is not clear whether the decrease in fatty acid oxidation results from ethanol per se, or from acetate derived from ethanol oxidation.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, O'Donnell et al perfused rabbit hearts with recirculating buffer containing 5 mM glucose, 0.5 mM [2,4,6,8,10,12,14, C]palmitate ± 0.1 mM unlabeled butyrate, a four carbon short chain fatty acid, the oxidation of which is not regulated by the carnitine palmitoyltransferase system. Using the NMR-assayed labeling of C4 of glutamate as a proxy for the labeling of mitochondrial acetyl-CoA, they found that palmitate oxidation was completely inhibited by 0.1 mM butyrate [16].…”

Section: Introductionmentioning

confidence: 99%

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Competition between acetate and oleate for the formation of malonyl-CoA and mitochondrial acetyl-CoA in the perfused rat heart

Bian¹,

Kasumov²,

Jobbins³

et al. 2006

Journal of Molecular and Cellular Cardiology

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We previously showed that in the perfused rat heart, the capacity of n-fatty acids to generate mitochondrial acetyl-CoA decreases as their chain length increases. In the present study, we investigated whether the oxidation of a long-chain fatty acid, oleate, is inhibited by short-chain fatty acids, acetate or propionate (which do and do not generate mitochondrial acetyl-CoA, respectively). We perfused rat hearts with buffer containing 4 mM glucose, 0.2 mM pyruvate, 1 mM lactate, and various concentrations of either (i) [U-13 C]acetate, (ii) [U-13 C]acetate plus [1-13 C]oleate, or (iii) unlabeled propionate plus [1-13 C]oleate. Using mass isotopomer analysis, we determined the contributions of the labeled substrates to the acetyl moiety of citrate (a probe of mitochondrial acetylCoA) and to malonyl-CoA. We found that acetate, even at low concentration, markedly inhibits the oxidation of [1-13 C]oleate in the heart, without change in malonyl-CoA concentration. We also found that propionate, at a concentration higher than 1 mM, decreases (i) the contribution of [1-13 C]oleate to mitochondrial acetyl-CoA, and (ii) malonyl-CoA concentration. The inhibition by acetate or propionate of acetyl-CoA production from oleate probably results from a competition for mitochondrial CoA between the CoA-utilizing enzymes.

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