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
- antioxidancia metabolismus MeSH
- energetický metabolismus MeSH
- folikulární buňky účinky léků metabolismus MeSH
- lidé MeSH
- metabolismus lipidů MeSH
- metabolismus sacharidů MeSH
- nebezpečné látky toxicita MeSH
- oocyty růst a vývoj metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy 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
- hepatocyty cytologie účinky léků MeSH
- játra cytologie MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- liraglutid farmakologie MeSH
- potkani Wistar MeSH
- separace buněk * MeSH
- ztučnělá játra patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články 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.
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
- glukagonu podobný peptid 1 analogy a deriváty MeSH
- hepatektomie trendy MeSH
- krysa rodu rattus MeSH
- liraglutid farmakologie MeSH
- peptidy farmakologie MeSH
- potkani Wistar MeSH
- regenerace jater účinky léků fyziologie MeSH
- živočišné jedy farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Klíčová slova
- léčba DM založená na inkretinech,
- MeSH
- aminokyseliny, peptidy a proteiny fyziologie metabolismus sekrece MeSH
- beta-buňky * enzymologie metabolismus sekrece MeSH
- dipeptidylpeptidasa 4 farmakologie metabolismus sekrece MeSH
- enteroendokrinní buňky cytologie enzymologie metabolismus MeSH
- glukagonu podobný peptid 1 * fyziologie metabolismus sekrece MeSH
- inkretiny fyziologie izolace a purifikace metabolismus MeSH
- inzulin * fyziologie izolace a purifikace sekrece MeSH
- L buňky (buněčná linie) fyziologie metabolismus účinky léků MeSH
- Langerhansovy ostrůvky cytologie fyziologie sekrece MeSH
- lidé MeSH
- lipidy fyziologie sekrece MeSH
- mastné kyseliny fyziologie sekrece MeSH
- nervový systém enzymologie metabolismus sekrece MeSH
- potravní vláknina metabolismus využití MeSH
- sacharidy fyziologie sekrece MeSH
- statistika jako téma MeSH
- tenké střevo enzymologie fyziologie sekrece MeSH
- žlučové kyseliny a soli fyziologie metabolismus sekrece MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem 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.
- Klíčová slova
- metabolizmus lipidů, metabolizmus sacharidů, jaterní steatóza, non-alcoholic fatty liver disease,
- MeSH
- glukagonu podobný peptid 1 * farmakologie metabolismus terapeutické užití MeSH
- inkretiny dějiny terapeutické užití MeSH
- játra * metabolismus účinky léků MeSH
- lidé MeSH
- metabolismus lipidů fyziologie účinky léků MeSH
- metabolismus sacharidů fyziologie účinky léků MeSH
- ztučnělá játra farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
