Caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin-sensitive cells through mechanisms implicating activation of AMPK
Context: Caffeic acid methyl (CAME) and ethyl (CAEE) esters stimulate glucose uptake and AMP-activated protein kinase (AMPK) in C2C12 myocytes (ATCC® CRL-1772TM). Objective: Effects of CAME and CAEE were now assessed on myocyte glucose transporter GLUT4 activity and expression, on hepatic gluconeoge...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-01-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/13880209.2017.1345952 |
| _version_ | 1819230650712981504 |
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| author | Hoda M. Eid Farah Thong Abir Nachar Pierre S. Haddad |
| author_facet | Hoda M. Eid Farah Thong Abir Nachar Pierre S. Haddad |
| author_sort | Hoda M. Eid |
| collection | DOAJ |
| description | Context: Caffeic acid methyl (CAME) and ethyl (CAEE) esters stimulate glucose uptake and AMP-activated protein kinase (AMPK) in C2C12 myocytes (ATCC® CRL-1772TM). Objective: Effects of CAME and CAEE were now assessed on myocyte glucose transporter GLUT4 activity and expression, on hepatic gluconeogenesis and on adipogenesis as well as major underlying signaling pathways. Materials and methods: GLUT4 protein translocation was studied in L6 GLUT4myc cells, glucose-6-phospatase (G6Pase) in H4IIE hepatocytes and adipogenesis in 3T3-L1 adipocytes. Key modulators were measured using western immunoblot. Cells were treated for 18 h with either CAME or CAEE at various concentrations (12.5–100 μM). Results: Myocyte glucose uptake rose from 10.1 ± 0.5 to 18.7 ± 0.8 and 21.9 ± 1.0 pmol/min/mg protein in DMSO-, CAME- and CAEE-stimulated cells, respectively, similar to insulin (17.7 ± 1.2 pmol/min/mg protein), while GLUT4myc translocation increased significantly by 1.70 ± 0.18, by 1.73 ± 0.18- and by 1.95 ± 0.30-fold (relative to DMSO), following insulin, CAME and CAEE stimulation, respectively. CAME and CAEE suppressed hepatocyte G6Pase by 62.0 ± 6.9% and 62.7 ± 6.0% with IC50 of 45.93 and 22.64 μM, respectively, comparable to insulin (70.7 ± 2.3% inhibition). Finally, CAME and CAEE almost abrogated adipogenesis (83.3 ± 7.2% and 97.3 ± 3.0% at 100 μM; IC50 of 13.8 and 12.9 μM, respectively). The compounds inhibited adipogenic factors C/EBP-β and PPAR-γ and stimulated AMPK activity in the three cell-lines. Discussion and conclusions: CAME and CAEE exerted antidiabetic activities in insulin-responsive cells through insulin-independent mechanisms involving AMPK and adipogenic factors. |
| first_indexed | 2024-12-23T11:32:27Z |
| format | Article |
| id | doaj.art-5dedaaeae6ad4263a9d40b0d2bb5b0c0 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-23T11:32:27Z |
| publishDate | 2017-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-5dedaaeae6ad4263a9d40b0d2bb5b0c02022-12-21T17:48:45ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162017-01-015512026203410.1080/13880209.2017.13459521345952Caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin-sensitive cells through mechanisms implicating activation of AMPKHoda M. Eid0Farah Thong1Abir Nachar2Pierre S. Haddad3Université de MontréalUniversity of TorontoUniversité de MontréalUniversité de MontréalContext: Caffeic acid methyl (CAME) and ethyl (CAEE) esters stimulate glucose uptake and AMP-activated protein kinase (AMPK) in C2C12 myocytes (ATCC® CRL-1772TM). Objective: Effects of CAME and CAEE were now assessed on myocyte glucose transporter GLUT4 activity and expression, on hepatic gluconeogenesis and on adipogenesis as well as major underlying signaling pathways. Materials and methods: GLUT4 protein translocation was studied in L6 GLUT4myc cells, glucose-6-phospatase (G6Pase) in H4IIE hepatocytes and adipogenesis in 3T3-L1 adipocytes. Key modulators were measured using western immunoblot. Cells were treated for 18 h with either CAME or CAEE at various concentrations (12.5–100 μM). Results: Myocyte glucose uptake rose from 10.1 ± 0.5 to 18.7 ± 0.8 and 21.9 ± 1.0 pmol/min/mg protein in DMSO-, CAME- and CAEE-stimulated cells, respectively, similar to insulin (17.7 ± 1.2 pmol/min/mg protein), while GLUT4myc translocation increased significantly by 1.70 ± 0.18, by 1.73 ± 0.18- and by 1.95 ± 0.30-fold (relative to DMSO), following insulin, CAME and CAEE stimulation, respectively. CAME and CAEE suppressed hepatocyte G6Pase by 62.0 ± 6.9% and 62.7 ± 6.0% with IC50 of 45.93 and 22.64 μM, respectively, comparable to insulin (70.7 ± 2.3% inhibition). Finally, CAME and CAEE almost abrogated adipogenesis (83.3 ± 7.2% and 97.3 ± 3.0% at 100 μM; IC50 of 13.8 and 12.9 μM, respectively). The compounds inhibited adipogenic factors C/EBP-β and PPAR-γ and stimulated AMPK activity in the three cell-lines. Discussion and conclusions: CAME and CAEE exerted antidiabetic activities in insulin-responsive cells through insulin-independent mechanisms involving AMPK and adipogenic factors.http://dx.doi.org/10.1080/13880209.2017.1345952adipogenesisakthepatic glucose outputinsulin resistanceglut4 |
| spellingShingle | Hoda M. Eid Farah Thong Abir Nachar Pierre S. Haddad Caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin-sensitive cells through mechanisms implicating activation of AMPK Pharmaceutical Biology adipogenesis akt hepatic glucose output insulin resistance glut4 |
| title | Caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin-sensitive cells through mechanisms implicating activation of AMPK |
| title_full | Caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin-sensitive cells through mechanisms implicating activation of AMPK |
| title_fullStr | Caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin-sensitive cells through mechanisms implicating activation of AMPK |
| title_full_unstemmed | Caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin-sensitive cells through mechanisms implicating activation of AMPK |
| title_short | Caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin-sensitive cells through mechanisms implicating activation of AMPK |
| title_sort | caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin sensitive cells through mechanisms implicating activation of ampk |
| topic | adipogenesis akt hepatic glucose output insulin resistance glut4 |
| url | http://dx.doi.org/10.1080/13880209.2017.1345952 |
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