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

Abstract

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...

Sequential changes in redox status and nitric oxide synthases expression in the liver after bile duct ligation

“…These changes do not seem to be progressive as there are not differences between rats 17 and 31 days after BDL. These observations are in agreement with those of several authors (Muriel et al, 1994;Krähenbühl et al, 1996). These animals also show portal hypertension that we determine indirectly through increase of splenic pressure and weight.…”

Hepatic carbohydrate metabolism in rats after laparotomy and laparoscopy

“…Glucagon as well as catecholamines (noradrenalin and adrenalin) are known to trigger glycogenolysis via activation of phosphorylase A and to decrease glycogen synthesis by inhibiting glycogen synthase, leading to a reduction of the hepatic glycogen stores [5]. In a previous study, we showed that the plasma levels of glucagon and catecholamines increase after laparotomy [26,27,30]. The observed decrease in the hepatic glycogen stores after laparotomy is therefore most likely the consequence of a more accentuated stress response in comparison to laparoscopy.…”

“…A decrease in the hepatic glycogen content has been shown to be associated with impaired glycogenolysis in perfused rat livers [26] and could therefore lead to reduced plasma glucose concentrations. As shown in Fig.…”

“…Starvation and markedly reduced intake of food for 24 h or longer are well-known to decrease the hepatic glycogen stores due to increased glycogenesis to maintain the plasma glucose concentrations in a physiological range [3,12,26,27,32]. Refeeding after starvation replenishes the hepatic glycogen stores within at least 2 days [12].…”

Transcriptional reprogramming in murine liver defines the physiologic consequences of biliary obstruction

“…In addition to hepatic fibrosis, chronic biliary obstruction results in deranged hepatic energy metabolism and increased oxidative stress [42,43]. Among the adaptive responses was an activation of the pentose phosphate pathway and up-regulation of the anti-oxidant glutathione S-transferase.…”