GLUT4
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Glucose is molecule usually studied in relation to metabolism. Except for this traditional view, it is known that under certain conditions glucose can serve as a signal molecule for the circadian system. The circadian system is entrained by relevant synchronizing cues that can be tissue-dependent. Central oscillator is synchronized mainly by light-dark cycle, while peripheral oscillators can be entrained by food intake. Glucose transport in the organism is controlled by insulin dependent and independent mechanism. Therefore, we employed streptozotocin-induced diabetes to elucidate the influence of metabolic changes on glucose transporter (glut1, glut4) 24-h expression profile in peripheral oscillators in tissues, inside (frontal cortex, cerebellum) and outside (heart) the blood-brain barrier. Diabetes was induced by streptozotocin injection. Seventeen days later, sampling was performed during a 24-h cycle. Gene expression was measured using real-time PCR. We observed down-regulation of glut1 and glut4 expression in the heart of diabetic rats. The expression of glut1 and glut4 in brain areas was not down-regulated, however, we observed trend to phase advance in glut1 expression in the cerebellum. These results may indicate higher glucose levels in diabetic brain, which might influence regulation of clock gene expression in different manner in brain compared to periphery.
- MeSH
- cirkadiánní hodiny * MeSH
- cirkadiánní rytmus * MeSH
- experimentální diabetes mellitus chemicky indukované metabolismus MeSH
- glukosa metabolismus MeSH
- hematoencefalická bariéra metabolismus MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- přenašeč glukosy typ 1 metabolismus MeSH
- přenašeč glukosy typ 4 metabolismus MeSH
- streptozocin MeSH
- tkáňová distribuce účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- glukosa metabolismus MeSH
- inzulin krev MeSH
- krysa rodu rattus MeSH
- proteiny přenášející monosacharidy metabolismus MeSH
- thyroxin farmakologie krev MeSH
- tukové buňky metabolismus účinky léků MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- diabetes mellitus MeSH
- finanční podpora výzkumu jako téma MeSH
- glukosa metabolismus MeSH
- krysa rodu rattus MeSH
- membránové glykoproteiny fyziologie patofyziologie MeSH
- myokard metabolismus MeSH
- srdce fyziologie MeSH
- svaly fyziologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
In this study, lipoic acid and heat shock treatments were applied to C(2)C(12) myotubes and Sprague-Dawley rats to investigate changes in the heat shock protein 70 (HSP70) and glucose transporter 4 (GLUT4) in 4 different skeletal muscle groups. The results of western blotting indicated that treatment of lipoic acid for 24 h, heat-shock and combined lipoic acid and heat-shock which all increased the level of HSP70 substantially in C(2)C(12) myotubes. However, either lipoic acid or heat-shock did not increase the level of GLUT4 in C(2)C(12) myotubes. In an in vitro migration assay, lipoic acid increased wound migration only when it was applied for 3 h. Moreover, our in vivo results revealed that lipoic acid did not increase HSP70 and GLUT4 in all 4 different skeletal muscles. Furthermore, heat-shock increased HSP70 in all 4 different muscle groups, and heat-shock treatment alone increased the GLUT4 in the soleus muscle only, suggesting that the GLUT4 increased by heat-shock was slow-twitch muscle specific. Collectively, our results indicated that heat-shock is critical factor that modulates GLUT4 and HSP70 in the skeletal muscle of rats.
- MeSH
- buněčné linie MeSH
- kosterní svaly fyziologie MeSH
- krysa rodu rattus MeSH
- potkani Sprague-Dawley MeSH
- přenašeč glukosy typ 4 metabolismus MeSH
- proteiny tepelného šoku HSP70 metabolismus MeSH
- reakce na tepelný šok fyziologie MeSH
- svalová vlákna typu I fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Adiposis is reputed as a twin disease of type 2 diabetes and greatly harmful to human health. In order to understand the molecular mechanisms of adiposis, the changes of physiological, pathological, epigenetic and correlative gene expression were investigated during the adiposis development of C57BL/6J mice induced by long time (9 months) high-fat and high-sucrose diet (HFSD) sustainably. The results showed that mRNA transcription level of the Leptin, Glut4 and Glut2 genes have been obviously changed, which exhibit a negative correlation with methylation on their promoter DNA. The results also revealed that HFSD induced higher level of DNA methyltransferase 1 (DNMT1) in fat tissue might play important role in regulating the changes of methylation pattern on Glut4 and Leptin genes, and which might be one of the molecular mechanisms for the adiposis development.
- MeSH
- adipozita fyziologie MeSH
- časové faktory MeSH
- dieta s vysokým obsahem tuků škodlivé účinky trendy MeSH
- DNA-(cytosin-5)-methyltransferasa 1 metabolismus MeSH
- játra metabolismus patologie MeSH
- konzumní sacharóza škodlivé účinky MeSH
- leptin metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- přenašeč glukosy typ 4 metabolismus MeSH
- tuková tkáň metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The purpose of the present study was to investigate whether peripheral brain-derived neurotrophic factor (BDNF) treatment induced metabolic adaptations in mouse skeletal muscle. BDNF (20 mg/kg/day) was injected subcutaneously for successive 14 days. BDNF treatment significantly reduced the total food intake and inhibited the weight gain in comparison to the control group. The glucose transporter 4 (GLUT4) protein expression in the gastrocnemius muscle was significantly increased by BDNF treatment in comparison to the control and pair-fed groups. Neither the oxidative nor the glycolytic enzyme activities in the gastrocnemius muscle changed after the BDNF treatment. These results suggest that the peripheral BDNF treatment promotes the skeletal muscle GLUT4 protein expression as well as hypophagia.
- MeSH
- časové faktory MeSH
- financování organizované MeSH
- hmotnostní přírůstek účinky léků MeSH
- injekce subkutánní MeSH
- kosterní svaly enzymologie metabolismus účinky léků MeSH
- mozkový neurotrofický faktor aplikace a dávkování MeSH
- myši inbrední ICR MeSH
- myši MeSH
- přenašeč glukosy typ 4 metabolismus MeSH
- přijímání potravy účinky léků MeSH
- up regulace MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
INTRODUCTION: Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. is used in traditional medicine for various purposes. Previous phytochemical studies focused on phenolic compounds, but triterpenoids were almost overlooked. OBJECTIVE: The study focused on the isolation of compounds with dual antidiabetic activity from the aerial parts of Z. clinopodioides subsp. bungeana. MATERIALS AND METHODS: Separation of CHCl3-soluble fraction by silica gel column chromatography using different mobile phases and purification of compounds by semi-preparative HPLC or preparative TLC. The structures of pure compounds were elucidated by 1D and 2D NMR experiments along with HRMS. Compound 1 was additionally identified by the single crystal X-ray diffraction method. α-Glucosidase inhibitory assay and GLUT4 expression and translocation in C2C12 myotubes were conducted to evaluate antidiabetic potential of isolated compounds. RESULTS: This phytochemical study led to the isolation of 20 compounds, including a unique monoterpene diperoxy dimer (1). Compounds 7 and 9-11 displayed more potent α-glucosidase inhibitory activity (IC50 45.3-135.3 μM) than acarbose used as a positive control (IC50 264.7 μM), while only pomolic acid (5) increased GLUT4 translocation in C2C12 myotubes in a significant manner. CONCLUSION: Extensive chromatographic separation led to the isolation and identification of a unique monoterpene diperoxy dimer (1) from aerial parts of Z. clinopodioides subsp. bungeana. Some triterpenes inhibited α-glucosidase, another increased GLUT4 translocation. Although none of the isolated compounds demonstrated dual antidiabetic activity, selected triterpenes proved to be potent antidiabetic agents in vitro.
- MeSH
- alfa-glukosidasy metabolismus MeSH
- buněčné linie MeSH
- hluchavkovité * chemie MeSH
- hypoglykemika * farmakologie chemie izolace a purifikace MeSH
- inhibitory glykosidových hydrolas farmakologie izolace a purifikace chemie MeSH
- myši MeSH
- nadzemní části rostlin chemie MeSH
- přenašeč glukosy typ 4 metabolismus MeSH
- rostlinné extrakty chemie farmakologie MeSH
- triterpeny * farmakologie chemie izolace a purifikace MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH