Chronic Alcohol Consumption Yields Sex Differences in Whole-Body Glucose Production in Rats

Sumida, Ken D.; Qureshi, Tauseef; Catanzaro, Michael J.; Arimoto, Steven M.; Hill, J. M.

doi:10.1093/alcalc/agh082

Cited by 9 publications

(20 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, ethanol fed male animals were able to match more closely the marked declines in glucose production with comparable reductions in glucose disappearance. 36 Consistent with the observations in humans, our ethanol fed female animals demonstrated higher plasma alcohol levels. As such, we cannot rule out the possibility that the higher amount of circulating alcohol caused the dramatic fall in glucose production and/or the failure to appropriately lower peripheral glucose clearance.…”

Section: Evidence For Sex Differences In Liver Glucose Outputsupporting

confidence: 91%

“…The decrease in glucose production was supported by the apparent rates of glucose carbon recycling which were significantly lower for ethanol fed females and occurred at an earlier onset compared to male and female controls. 36 In contrast, ethanol fed males similarly had lower glucose production and apparent rates of glucose carbon recycling, but its occurrence was delayed compared to ethanol fed females. Further, ethanol fed male animals were able to match more closely the marked declines in glucose production with comparable reductions in glucose disappearance.…”

Section: Evidence For Sex Differences In Liver Glucose Outputmentioning

confidence: 94%

“…We subsequently injected an equivalent alcohol dose (4 g/kg) into all chronic ethanol fed animals and corresponding controls where we followed the impact of alcohol on blood glucose levels over a 1-hour period. 36 Following 8 weeks of chronic alcohol consumption, the female animals chronically fed the ethanol diet had significantly lower blood glucose levels prior to and after the injection of alcohol compared to all other groups (figure 1). Under these circumstances, hepatic glycogen stores were essentially depleted making gluconeogenesis the primary mode to resist the fall in blood glucose concentration.…”

Section: Evidence For Sex Differences In Liver Glucose Outputmentioning

confidence: 95%

“…36 In contrast to Winston and Reitz, 31 we used Wistar rats to take into account any impact attributable to the location of hepatic ADH between males versus females. We also employed a 48-hour fast to deplete hepatic glycogen stores.…”

Section: Evidence For Sex Differences In Liver Glucose Outputmentioning

confidence: 99%

“…A thorough examination of our prior studies 36,48,49 will reveal several limitations that we acknowledge. Further, our studies primarily focused on the liver.…”

Section: Glucose Homeostasis -Implications For Alcoholicsmentioning

confidence: 99%

See 4 more Smart Citations

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

Sumida

Hill

Matveyenko³

2007

Clinical Medicine & Research

View full text Add to dashboard Cite

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.

show abstract

Section: Evidence For Sex Differences In Liver Glucose Outputsupporting

confidence: 91%

Section: Evidence For Sex Differences In Liver Glucose Outputmentioning

confidence: 94%

Section: Evidence For Sex Differences In Liver Glucose Outputmentioning

confidence: 95%

Section: Evidence For Sex Differences In Liver Glucose Outputmentioning

confidence: 99%

“…A thorough examination of our prior studies 36,48,49 will reveal several limitations that we acknowledge. Further, our studies primarily focused on the liver.…”

Section: Glucose Homeostasis -Implications For Alcoholicsmentioning

confidence: 99%

See 3 more Smart Citations

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

Sumida

Hill

Matveyenko³

2007

Clinical Medicine & Research

View full text Add to dashboard Cite

show abstract

Simultaneous determination of blood glucose and isoleucine levels in rats after chronic alcohol exposure by microwave‐assisted derivatization and isotope dilution gas chromatography/mass spectrometry

Xue

Zhang

Deng

et al. 2007

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

Blood glucose and isoleucine are two biomarkers of chronic alcohol exposure. Simultaneous determination of blood glucose and isoleucine levels helps to illuminate the influence of alcohol on the metabolism of glucose and amino acids. The most accurate method for the detection of serum glucose is isotope dilution gas chromatography/mass spectrometry (ID GC/MS). In this study, a rapid, simple and sensitive technique was developed for the quantitative analysis of glucose and isoleucine in rats after chronic alcohol exposure by microwave-assisted derivatization (MAD) and ID GC/MS. Serum glucose and isoleucine were rapidly derivatized by N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) with microwave irradiation, and the trimethylsilyl derivatives were analyzed by GC/MS. This technique was used to demonstrate that pyrroloquinoline quinone (PQQ), a non-covalently bound prosthetic group in some quinoproteins involved in the metabolism of some sugar or alcohol, could reverse alcohol exposure induced glucose elevation. On the other hand, it did not affect the metabolism of isoleucine whose level was elevated along with serum glucose. The combination of MAD and ID GC/MS has been shown to be an accurate, rapid, simple and sensitive method for the quantification of glucose and isoleucine in serum samples.

show abstract

Alcohol-induced suppression of gluconeogenesis is greater in ethanol fed female rat hepatocytes than males

Sumida

Cogger

Matveyenko

2007

Alcohol

Self Cite

View full text Add to dashboard Cite

The impact of alcohol-induced suppression on hepatic gluconeogenesis (HGN) after chronic ethanol consumption between males and females is unknown. To determine the effects of chronic alcohol consumption (8 weeks) on HGN, the isolated hepatocyte technique was used on 24 h fasted male and female Wistar rats. Livers were initially perfused with collagenase and the hepatocytes were isolated. Aliquots of the cell suspension were placed in Krebs-Henseleit buffer and incubated for 30 min with lactate, [U -14C]lactate, and nine different concentrations of ethanol (EtOH). Dose-effect curves were generated for the determination of maximal and half-maximal alcohol-induced inhibition on HGN. There was no significant difference in HGN (lactate only and no EtOH) between males and females fed the control diet (88.5 +/- 5.1 nmol/mg protein/30 min). Similarly, the HGN (lactate only and no EtOH) in males fed the ethanol diet (ME) were not significantly different (82.8 +/- 3.5 nmol/mg protein/30 min) compared to controls. In contrast, the females chronically fed the ethanol diet (FE) had significantly (P < .05) lower HGN (67.8 +/- 4.6 nmol/mg protein/30 min) compared to both ME and controls. With alcohol in the incubation medium, the HGN significantly (P<.05) declined in all groups. While alcohol suppressed HGN to a larger (P < .05) extent in ME (45.8 +/- 3.7 nmol/mg protein/30 min) compared to controls (64.0 +/- 3.8 nmol/mg protein/30 min), the inhibition was even greater (P < .05) in FE (32.7 +/- 3.2 nmol/mg protein/30 min). The more pronounced effect of chronic alcohol consumption on HGN in the presence of ethanol in female hepatocytes was supported by the concomitant decreases (P < .05) in 14C-lactate incorporation into 14C-glucose, lactate uptake, and 14C-lactate uptake. The results suggest that chronic alcohol consumption elicits a greater reduction on HGN in the presence of ethanol in the hepatocytes of females compared to males.

show abstract

Chronic Alcohol Consumption Yields Sex Differences in Whole-Body Glucose Production in Rats

Abstract: Chronic alcohol consumption results in sex differences in whole-body glucose production and glucose regulation.

Cited by 9 publications

References 33 publications

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

Simultaneous determination of blood glucose and isoleucine levels in rats after chronic alcohol exposure by microwave‐assisted derivatization and isotope dilution gas chromatography/mass spectrometry

Alcohol-induced suppression of gluconeogenesis is greater in ethanol fed female rat hepatocytes than males

Contact Info

Product

Resources

About