Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis.

Owen, Oliver E.; Reichle, Frederick A.; Mozzoli, Maria; Kreulen, Thomas H.; Patel, Minu; Elfenbein, I. Bruce; Golsorkhi, M; Chang, Kyung Hyun; Rao, Nagaraj; Su-e, Han; Boden, Guenther

doi:10.1172/jci110240

Cited by 284 publications

(160 citation statements)

References 32 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…44 The depressed rate of glucose oxidation observed in fasting BC patients may reflect reduced hepatic glycogen capacity but appears not to be as exaggerated as the fasting profile observed in patients with HC cirrhosis, although this cannot be confirmed. The significant increase in postabsorptive rates of lipid oxidation found in HC patients is similar to that found by other investigators 1,45 and may be attributed to exhausted rather than depleted glycogen reserves. It is likely that this increased rate of lipid oxidation is an adaptive process, acting to offset the reduction in energy normally available through glycogenolysis.…”

Section: Discussionsupporting

confidence: 89%

Macronutrient Preference, Dietary Intake, and Substrate Oxidation Among Stable Cirrhotic Patients

et al. 1999

View full text Add to dashboard Cite

Anorexia in liver disease is common; however, its association with aberrant metabolism and the type of cirrhosis has not been considered. Dietary intake, nutritional status, fasting substrate oxidation, and macronutrient preference were examined in controls (n ‫؍‬ 18) and 65 patients with hepatocellular (n ‫؍‬ 31) or biliary cirrhosis (n ‫؍‬ 34). Energy intakes were lowest in hepatocellular patients (

show abstract

Section: Discussionsupporting

confidence: 89%

Macronutrient Preference, Dietary Intake, and Substrate Oxidation Among Stable Cirrhotic Patients

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Fig-A reduction in the hepatic glycogen content has also been ure 3 illustrates that the active fraction of glycogen synthase described in humans with alcohol-induced cirrhosis 1 and in shows a negative correlation with the plasma glucagon con-rats with CCl 4 -induced cirrhosis, 7,8 but not in humans or excentration. No significant correlation was found between the perimental animals with long-term cholestasis.…”

Section: Methodsmentioning

confidence: 88%

Progressive decrease in tissue glycogen content in rats with long-term cholestasis

et al. 1996

View full text Add to dashboard Cite

show a reduction in nonoxidative glucose metabolism, 3,4 findLiver and skeletal muscle glycogen metabolism were ings compatible with impaired glycogen synthesis. 5 In supinvestigated in rats 1 and 4 weeks after bile duct ligation port of this concept, glycogen synthase activity has been (BDL) and in pair-fed, sham-operated control rats. Livfound to be reduced in skeletal muscle from cirrhotic paers were subjected to morphometric analysis to express tients. 5 Similarly, in rats with carbon tetrachloride (CCl 4 )-glycogen content and enzyme activities per mL hepatoinduced cirrhosis, incorporation of [ 14 C]-glucose into glycogen cytes. One week after BDL, the hepatic glycogen content in skeletal muscle and diaphragm was reduced, suggesting was 28.8 { 13.8 versus 38.6 { 16.4 mg/mL hepatocyte in impaired glycogen synthesis. 6 In addition, in rats with CCl 4 -BDL and control rats, respectively. Total activity of glyinduced cirrhosis, the hepatic glycogen content has been decogen synthase (50.2 { 7.0 vs. 63.5 { 9.4 mU/mL hepatoscribed to be reduced per gram liver and per hepatocyte cytes) and glycogen phosphorylase (59.4 { 12.9 vs. 90.8 { 18.9 U/mL) were significantly reduced in BDL whereas whereas skeletal muscle glycogen content was unchanged as the active fraction of glycogen synthase (27 { 6 vs. 38 { compared with pair-fed control rats. 7 During starvation, rats 5%) but not of glycogen phosphorylase was reduced. The with CCl 4 -induced cirrhosis lost their hepatic glycogen stores skeletal muscle glycogen content was not different be-more rapidly than control rats, 7,8 a finding which was accomtween BDL and control rats. Four weeks after BDL, he-panied by a faster increase in acylcarnitines and nonesteripatic glycogen content was further reduced (20.5 { 14.2 fied fatty acids in plasma, suggesting an accelerated transivs. 52.9 { 6.4 mg/mL). Total activity of glycogen synthase tion from the fed to the fasted state thereby explaining the (38.8 { 12.1 vs. 60.1 { 4.6 mU/mL hepatocytes) and glyco-preferential use of fatty acids as a fuel in cirrhosis. 7 gen phosphorylase (127 { 19 vs. 178 { 33 U/mL hepato-The mechanisms leading to reduced hepatic and skeletal cytes) were both reduced in BDL rats as were their cor-muscle glycogen stores in animals and humans with cirrhosis responding active fractions (30 { 18 vs. 66 { 8% and 58 are not clear so far. Because of the complexity of its regula-{ 10 vs. 76 { 10). At this time point, the glycogen content tion, there are many possible mechanisms whereby glycogen in soleus muscle was decreased by 64% in BDL. The glu-metabolism could be disturbed in humans or animals with cagon plasma concentration was increased in BDL rats cirrhosis. Glycogen synthase and phosphorylase are the two at both time points. There were positive correlations be-key enzymes responsible for glycogen synthesis and glycogentween the volume fraction and both hepatic glycogen olysis, respectively. The activities of these enzymes are concontent and total activity of hepatic glycogen synthase. trolled by phosphor...

show abstract

“…A seemingly paradoxical observation in patients with alcohol-induced liver cirrhosis is an elevation in HGN capacity. 28,29 Further, heavy ethanol ingestion for a prolonged period of time may also contribute to abdominal obesity and an increased risk for type 2 diabetes. 30 Therefore, we have two contrasting effects related to alcohol consumption.…”

Section: Evidence For Sex Differences In Liver Glucose Outputmentioning

confidence: 99%

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

Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis.

Cited by 284 publications

References 32 publications

Macronutrient Preference, Dietary Intake, and Substrate Oxidation Among Stable Cirrhotic Patients

Macronutrient Preference, Dietary Intake, and Substrate Oxidation Among Stable Cirrhotic Patients

Progressive decrease in tissue glycogen content in rats with long-term cholestasis

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

Contact Info

Product

Resources

About