Metabolic heterogeneity of glycogen in hepatocytes of patients with liver cirrhosis: the glycogen of the liver lobule zones in cirrhosis

Kudryavtseva, M.V.; Bezborodkina, Natalia N.; Okovity, Sergey V.; Kudryavtsev, B. N.

doi:10.1097/00042737-200106000-00013

Cited by 12 publications

(11 citation statements)

References 12 publications

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“…The activity of GS in the cirrhotic rat liver did not differ from the control values. These data confirm the results of our previous studies [ 14 , 35 ] and suggest that the glycogen accumulation in hepatocytes may be associated with a decreased activity of the key enzyme of glycogenolysis, GPa.…”

Section: Discussionsupporting

confidence: 92%

Postprandial Glycogen Content Is Increased in the Hepatocytes of Human and Rat Cirrhotic Liver

Bezborodkina

Оковитый

Kudryavtsev

2021

Cells

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Chronic hepatitises of various etiologies are widespread liver diseases in humans. Their final stage, liver cirrhosis (LC), is considered to be one of the main causes of hepatocellular carcinoma (HCC). About 80–90% of all HCC cases develop in LC patients, which suggests that cirrhotic conditions play a crucial role in the process of hepatocarcinogenesis. Carbohydrate metabolism in LC undergoes profound disturbances characterized by altered glycogen metabolism. Unfortunately, data on the glycogen content in LC are few and contradictory. In this study, the material was obtained from liver biopsies of patients with LC of viral and alcohol etiology and from the liver tissue of rats with CCl4-induced LC. The activity of glycogen phosphorylase (GP), glycogen synthase (GS), and glucose-6-phosphatase (G6Pase) was investigated in human and rat liver tissue by biochemical methods. Total glycogen and its labile and stable fractions were measured in isolated individual hepatocytes, using the cytofluorometry technique of PAS reaction in situ. The development of LC in human and rat liver was accompanied by an increase in fibrous tissue (20- and 8.8-fold), an increase in the dry mass of hepatocytes (by 25.6% and 23.7%), and a decrease in the number of hepatocytes (by 50% and 28%), respectively. The rearrangement of the liver parenchyma was combined with changes in glycogen metabolism. The present study showed a significant increase in the glycogen content in the hepatocytes of the human and the rat cirrhotic liver, by 255% and 210%, respectively. An increased glycogen content in cells of the cirrhotic liver can be explained by a decrease in glycogenolysis due to a decreased activity of G6Pase and GP.

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Section: Discussionsupporting

confidence: 92%

Postprandial Glycogen Content Is Increased in the Hepatocytes of Human and Rat Cirrhotic Liver

Bezborodkina

Оковитый

Kudryavtsev

2021

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“…Meanwhile, exogenous control mechanisms are accomplished by biochemical interactions between the liver and the musculature, as well as interactions among the renal, enteric and endocrine systems 3 . The metabolic heterogeneity of hepatocytes in health and disease is summarized elsewhere [5][6][7] . Routine clinical evaluation of the functional status of hepatocytes, the socalled liver function test (LFT)/biliary integrity test (BIT), is established by evaluating activities of nonfunctional plasma enzyme indicators, namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and the inducible hepatocyte smooth endoplasmic reticulum (SER) specific enzyme, γ-glutamyl transferase (γ-GT).…”

Section: Introductionmentioning

confidence: 99%

Acute dysfunctional status of hepatorenal tissues of rats administered with leaf extracts of Ocimum gratissimum L. (Lamiaceae)

et al. 2020

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Background: Given the vast medicinal properties of Ocimum gratissimum, the present study evaluated, in comparative terms, the acute dysfunctional status of hepatorenal tissues of Wistar rats administered with petroleum ether (PE) and ethyl acetate (EA) leaf extracts of O. gratissimum. Methods: Grouping of the experimental rats was assigned according to the treatments given, in which graded doses {200, 400, 600 and 800 mg/kg body weight (b.w.)} of PE and EA fractions of O. gratissimum leaf extract were administered to the rats by oral gavage on a daily basis for a period of 21 days. Serum levels of hepatorenal tissues biomarkers were measured using standard spectrophotometric methods. The organ-to-body weight ratio of the rats was measured on the 21st day of the experiment. Results: Serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (i.e. AST/ALT) of the experimental rat groups was found to be within the range of 0.919 – 1.022 unit. The experimental rat groups administered with PE and EA fractions of O. gratissimum leaf extract showed dose-dependent increasing levels of serum alkaline phosphatase (ALP) activity. Likewise, rat groups administered with the herbal extracts exhibited increasing serum total bilirubin, urea and creatinine concentrations, in a dose-dependent manner. At the end of the 21-day treatment period, all the experimental rat groups showed increase in body weight, ranging from 0.79 – 1.98% increase. The liver weight and kidney weight to body weight ratios were within the range of (0.0468 0.02 – 0.0981 0.04) unit and (0.00245 0.002 – 0.01968 0.007) unit, respectively. Conclusion: The results showed that doses of PE and EA fractions of O. gratissimum leaf extract greater than 400 mg/kg b.w. induced dose-dependent hepatorenal toxicity, with the EA fraction provoking greater toxicity than the PE fraction of O. gratissimum leaf extract.

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“…In a physiological glycogen synthesis, when fasted animals are administered with glucose, the stabile fraction is initially quickly increased, but then the labile fraction increases being responsible for the actual glycogen accumulation . In contrast, in a pathologic situation of liver cirrhosis, the stabile fraction is especially increased and the ratio of LF/SF decreased, suggesting a more stable increase in glycogen . It can be hypothesized that similar molecular changes in glycogen structure could also occur in diabetes, as similar disruptions in glycogen metabolism have been shown to occur in cirrhosis and diabetes, and α‐particles of glycogen have been shown to degrade more readily in diabetes .…”

Section: Introductionmentioning

confidence: 99%

“…18 In contrast, in a pathologic situation of liver cirrhosis, the stabile fraction is especially increased and the ratio of LF/SF decreased, suggesting a more stable increase in glycogen. [19][20][21][22] It can be hypothesized that similar molecular changes in glycogen structure could also occur in diabetes, as similar disruptions in glycogen metabolism have been shown to occur in cirrhosis and diabetes, 23 and a-particles of glycogen have been shown to degrade more readily in diabetes. 8 However, it is not known whether the structural changes contribute to the disease pathogenesis, and whether these changes could be targeted by drug therapy.…”

Section: Introductionmentioning

confidence: 99%

Metformin normalizes the structural changes in glycogen preceding prediabetes in mice overexpressing neuropeptide Y in noradrenergic neurons

Ailanen

Bezborodkina

Virtanen

et al. 2018

Pharmacology Res & Perspec

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Hepatic insulin resistance and increased gluconeogenesis are known therapeutic targets of metformin, but the role of hepatic glycogen in the pathogenesis of diabetes is less clear. Mouse model of neuropeptide Y (NPY) overexpression in noradrenergic neurons (OE‐NPYD βH) with a phenotype of late onset obesity, hepatosteatosis, and prediabetes was used to study early changes in glycogen structure and metabolism preceding prediabetes. Furthermore, the effect of the anti‐hyperglycemic agent, metformin (300 mg/kg/day/4 weeks in drinking water), was assessed on changes in glycogen metabolism, body weight, fat mass, and glucose tolerance. Glycogen structure was characterized by cytofluorometric analysis in isolated hepatocytes and mRNA expression of key enzymes by qPCR. OE‐NPYD βH mice displayed decreased labile glycogen fraction relative to stabile fraction (the intermediate form of glycogen) suggesting enhanced glycogen cycling. This was supported by decreased filling of glucose residues in the 10th outer tier of the glycogen molecule, which suggests accelerated glycogen phosphorylation. Metformin reduced fat mass gain in both genotypes, but glucose tolerance was improved mostly in wild‐type mice. However, metformin inhibited glycogen accumulation and normalized the ratio between glycogen structures in OE‐NPYD βH mice indicating decreased glycogen synthesis. Furthermore, the presence of glucose residues in the 11th tier together with decreased glycogen phosphorylase expression suggested inhibition of glycogen degradation. In conclusion, structural changes in glycogen of OE‐NPYD βH mice point to increased glycogen metabolism, which may predispose them to prediabetes. Metformin treatment normalizes these changes and suppresses both glycogen synthesis and phosphorylation, which may contribute to its preventive effect on the onset of diabetes.

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Metabolic heterogeneity of glycogen in hepatocytes of patients with liver cirrhosis: the glycogen of the liver lobule zones in cirrhosis

Cited by 12 publications

References 12 publications

Postprandial Glycogen Content Is Increased in the Hepatocytes of Human and Rat Cirrhotic Liver

Postprandial Glycogen Content Is Increased in the Hepatocytes of Human and Rat Cirrhotic Liver

Acute dysfunctional status of hepatorenal tissues of rats administered with leaf extracts of Ocimum gratissimum L. (Lamiaceae)

Metformin normalizes the structural changes in glycogen preceding prediabetes in mice overexpressing neuropeptide Y in noradrenergic neurons

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