Granulosa cells (GCs) are somatic cells essential for establishing and maintaining bi-directional communication with the oocytes. This connection has a profound importance for the delivery of energy substrates, structural components and ions to the maturing oocyte through gap junctions. Cumulus cells, group of closely associated GCs, surround the oocyte and can diminished the effect of harmful environmental insults. Both GCs and oocytes prefer different energy substrates in their cellular metabolism: GCs are more glycolytic, whereas oocytes rely more on oxidative phosphorylation pathway. The interconnection of these cells is emphasized by the fact that GCs supply oocytes with intermediates produced in glycolysis. The number of GCs surrounding the oocyte and their age affect the energy status of oocytes. This review summarises available studies collaboration of cellular types in the ovarian follicle from the point of view of energy metabolism, signaling and protection of toxic insults. A deeper knowledge of the underlying mechanisms is crucial for better methods to prevent and treat infertility and to improve the technology of in vitro fertilization.
- MeSH
- Antioxidants metabolism MeSH
- Energy Metabolism MeSH
- Granulosa Cells drug effects metabolism MeSH
- Humans MeSH
- Lipid Metabolism MeSH
- Carbohydrate Metabolism MeSH
- Hazardous Substances toxicity MeSH
- Oocytes growth & development metabolism MeSH
- Reactive Oxygen Species metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Non-alcoholic fatty liver disease and its complications are frequent causes of liver-related morbidity and mortality. Incretin glucagon-like peptide-1 (GLP-1) affects liver functions and metabolism. Although GLP-1 analogues are widely used in clinical practice, information regarding their potential toxic effect on hepatocytes in vitro is missing. Therefore, we evaluated the effect of GLP-1 analogue liraglutide on activity of caspases 3/7, cell viability and oxidative stress in primary cultures of hepatocytes. Primary cultures isolated from male Wistar rats fed a standard (ST1-group, 10% energy from fat) or a high-fat diet (HF-group, 71% fat) for 10 weeks were incubated with liraglutide (0.1-1000 nmol/l) for 24 h. Activities of caspases 3/7 and cellular dehydrogenases (WST-1), lactate dehydrogenase (LDH) leakage and oxidative stress (malondialdehyde concentration and DCFDA assay) were evaluated. HF-groups vs. ST1-groups showed higher caspases activity, LDH leakage and MDA production (p < 0.001) and lower cellular dehydrogenases activity (p < 0.01). Liraglutide induced a dose-dependent decrease of caspases activity in both groups, reduction of oxidative stress in HF-animals and exerted no negative effects on other parameters. In conclusion, GLP-1 analogue liraglutide decreased activity of caspases 3/7, reduced ROS production and didn't exhibit negative effects on cell viability and oxidative stress in primary cultures of hepatocytes isolated from lean and steatotic livers.
- MeSH
- Hepatocytes cytology drug effects MeSH
- Liver cytology MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Liraglutide pharmacology MeSH
- Rats, Wistar MeSH
- Cell Separation * MeSH
- Fatty Liver pathology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Numerous conditions, including cancer, diabetes, aging, and atherosclerosis, are thought to be associated with oxidative stress. Oxidative stress is defined as a persistent imbalance between oxidation and antioxidation, resulting in the damage of cellular macromolecules and is often considered to be involved in wide variety of human diseases. However, the current literature is very heterogeneous making it rather difficult to draw general conclusions. Often, different biomarkers have been used in different health problems. In addition, individual biomarkers are often measured using nonspecific methods. The development of informative and highly reliable markers is very important. The conflicting results of numerous studies, including clinical trials, make it clear that despite the explosion of studies performed in the last decades, leading to nutritional guidelines recommending consumption of food-related antioxidants, direct proof is still lacking.
- MeSH
- Biomarkers metabolism MeSH
- Cardiovascular Diseases metabolism MeSH
- Humans MeSH
- Mitochondria metabolism MeSH
- Oxidative Stress * MeSH
- Reactive Oxygen Species metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Glucagon-like peptide-1 (GLP-1) is an incretin known for proliferative and antiapoptotic effects on various tissues. Exenatide and Liraglutide are GLP-1 analogues used in clinical practice as antidiabetic drugs. Since GLP-1 and its analogues exert significant effect on liver metabolism and since changes in intermediary metabolism play an important role in the process of liver regeneration, we decided to determine the effect of Exenatide and Liraglutide on the early phase of liver regeneration and selected metabolic parameters in a model of 2/3 partial hepatectomy (PHx) in rats. Animals were submitted either to PHx or laparotomy and received 3 doses of either GLP-1 analogues (Exenatide - 42 microg/kg b.w., Liraglutide - 0.75 mg/kg b.w.) or saline intraperitoneally. We analyzed body and liver weight, liver bromodeoxyuridine incorporation, liver content of DNA, triacylglycerols and cholesterol and biochemical serum parameters. Bromodeoxyuridine labeling was significantly lower in hepatectomized rats receiving either type of GLP-1 analogues when compared to hepatectomized controls. This effect was more pronounced in the Liraglutide group compared to Exenatide (p<0.001). In addition, liver DNA content was lower in hepatectomized rats receiving Liraglutide than in hepatectomized control rats (p<0.001). In conclusion, GLP-1 analogues Exenatide and Liraglutide significantly inhibited an early phase of liver regeneration after PHx in rats. This inhibitory effect was more pronounced in rats receiving Liraglutide.
- MeSH
- Glucagon-Like Peptide 1 analogs & derivatives MeSH
- Hepatectomy trends MeSH
- Rats MeSH
- Liraglutide pharmacology MeSH
- Peptides pharmacology MeSH
- Rats, Wistar MeSH
- Liver Regeneration drug effects physiology MeSH
- Venoms pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Keywords
- léčba DM založená na inkretinech,
- MeSH
- Amino Acids, Peptides, and Proteins physiology metabolism secretion MeSH
- Insulin-Secreting Cells * enzymology metabolism secretion MeSH
- Dipeptidyl Peptidase 4 pharmacology metabolism secretion MeSH
- Enteroendocrine Cells cytology enzymology metabolism MeSH
- Glucagon-Like Peptide 1 * physiology metabolism secretion MeSH
- Incretins physiology isolation & purification metabolism MeSH
- Insulin * physiology isolation & purification secretion MeSH
- L Cells physiology metabolism drug effects MeSH
- Islets of Langerhans cytology physiology secretion MeSH
- Humans MeSH
- Lipids physiology secretion MeSH
- Fatty Acids physiology secretion MeSH
- Nervous System enzymology metabolism secretion MeSH
- Dietary Fiber metabolism utilization MeSH
- Carbohydrates physiology secretion MeSH
- Statistics as Topic MeSH
- Intestine, Small enzymology physiology secretion MeSH
- Bile Acids and Salts physiology metabolism secretion MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Problematika vztahu glucagon‑like peptide 1 (GLP‑1) k jaterním buňkám je velmi intenzivně studována. V rámci metabolizmu sacharidů stimuluje GLP‑1 tvorbu glykogenu a snižuje novotvorbu glukózy – působí tedy podobně jako inzulin. V oblasti metabolizmu lipidů se popisuje posílení oxidace mastných kyselin a odsunu lipidů z hepatocytů při souběžném snížení de novo lipogeneze – účinky více připomínající vliv glukagonu. Některé práce naznačují příznivý vliv GLP‑1 na oxidační stres, stres endoplazmatického retikula, produkci zánětlivých mediátorů či na dysfunkci biliární sekrece. Dosavadní výsledky napovídají, že léčiva ovlivňující inkretinový systém by v budoucnu mohla být využita v léčbě některých jaterních onemocnění, jako jsou např. NAFLD či NASH. V následujícím přehledu zmíníme dosud známé účinky GLP‑1 na jaterní funkce a jaterní metabolizmus a poukážeme na jeho možné budoucí terapeutické využití při léčbě jaterních onemocnění.
Effects of glucagon‑like peptide 1 (GLP‑1) on liver cells are very intensively studied. In the metabolism of saccharides GLP‑1 stimulates synthesis of glycogen and reduces glucose production – thus acting like insulin. In the lipid metabolism it enhances fatty acid oxidation and lipid transport from hepatocytes while reducing de novo lipogenesis – effects more similar to glucagon action. Some studies suggest beneficial effects of GLP‑1 on oxidative stress, endoplasmic reticulum stress, production of inflammatory mediators and dysfunction of biliary secretion. Current results suggest that drugs affecting incretin system could be used in the treatment of certain liver diseases (e.g. NAFLD and NASH) in the future. In the following article we mention the known effects of GLP‑1 on liver functions and liver metabolism and we point out its possible future therapeutic use in the treatment of liver diseases.
- Keywords
- metabolizmus lipidů, metabolizmus sacharidů, jaterní steatóza, non-alcoholic fatty liver disease,
- MeSH
- Glucagon-Like Peptide 1 * pharmacology metabolism therapeutic use MeSH
- Incretins history therapeutic use MeSH
- Liver * metabolism drug effects MeSH
- Humans MeSH
- Lipid Metabolism physiology drug effects MeSH
- Carbohydrate Metabolism physiology drug effects MeSH
- Fatty Liver drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH