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

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

Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates

Non-alcoholic fatty liver disease (NAFLD), or metabolic (dysfunction)-associated fatty liver disease (MAFLD), is characterized by high global incidence and prevalence, a tight association with common metabolic comorbidities, and a substantial risk of progression and associated mortality. Despite the increasingly high medical and socioeconomic burden of NAFLD, the lack of approved pharmacotherapy regimens remains an unsolved issue. In this paper, we aimed to provide an update on the rapidly changing therapeutic landscape and highlight the major novel approaches to the treatment of this disease. In addition to describing the biomolecules and pathways identified as upcoming pharmacological targets for NAFLD, we reviewed the current status of drug discovery and development pipeline with a special focus on recent evidence from clinical trials

doi:10.1078/0940-2993-00270

The effect of the actoprotector bemithyl (2-ethylthiobenzimidazole hydrobromide) on the content of glycogen and activities of glycogen synthase, glycogen phosphorylase, and glucose-6-phosphatase was studied in the cirrhotic rat liver. The content of glycogen and its fraction was determined by a cytofluorimetric method Introduction Chronic hepatitis and cirrhosis of various causes are among diseases that are the most dangerous for human health. Chronic effects of viruses or toxic substances produce a wide spectrum of liver damage. Treatment of these diseases is very difficult due both to the multiple effects of the damaging factors and to the necessity for this organ to perform its numerous functions continuously and effectively

Dynamics of the Glycogen β-Particle Number in Rat Hepatocytes during Glucose Refeeding

Glycogen is an easily accessible source of energy for various processes. In hepatocytes, it can be found in the form of individual molecules (β-particles) and their agglomerates (α-particles). The glycogen content in hepatocytes depends on the physiological state and can vary due to the size and number of the particles. Using biochemical, cytofluorometric, interferometric and morphometric methods, the number of β-particles in rat hepatocytes was determined after 48 h of fasting at different time intervals after glucose refeeding. It has been shown that after starvation, hepatocytes contain ~1.6 × 108 β-particles. During refeeding, their number of hepatocytes gradually increases and reaches a maximum (~5.9 × 108) at 45 min after glucose administration, but then quickly decreases. The data obtained suggest that in cells there is a continuous synthesis and degradation of particles, and at different stages of life, one or another process predominates. It has been suggested that in the course of glycogenesis, pre-existing β-particles are replaced by those formed de novo. The main contribution to the deposition of glycogen is made by an increase in the glucose residue number in its molecules. The average diameter of β-particles of glycogen during glycogenesis increases from ~11 nm to 21 nm