DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression
<p dir="ltr">Heat shock response (HSR) is an essential host-defense mechanism that is dysregulated in obesity-induced insulin resistance and type 2 diabetes (T2D). Our recent data demonstrated that DNAJB3 was downregulated in obese human subjects and showed negative correlation with...
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| مؤلفون آخرون: | , , , , , , , , |
| منشور في: |
2015
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| _version_ | 1864513557223178240 |
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| author | Mohamed Abu-Farha (25322) |
| author2 | Preethi Cherian (437070) Irina Al-Khairi (437069) Ali Tiss (437068) Abdelkrim Khadir (437074) Sina Kavalakatt (437073) Samia Warsame (437075) Mohammed Dehbi (309033) Kazem Behbehani (412126) Jehad Abubaker (437067) |
| author2_role | author author author author author author author author author |
| author_facet | Mohamed Abu-Farha (25322) Preethi Cherian (437070) Irina Al-Khairi (437069) Ali Tiss (437068) Abdelkrim Khadir (437074) Sina Kavalakatt (437073) Samia Warsame (437075) Mohammed Dehbi (309033) Kazem Behbehani (412126) Jehad Abubaker (437067) |
| author_role | author |
| dc.creator.none.fl_str_mv | Mohamed Abu-Farha (25322) Preethi Cherian (437070) Irina Al-Khairi (437069) Ali Tiss (437068) Abdelkrim Khadir (437074) Sina Kavalakatt (437073) Samia Warsame (437075) Mohammed Dehbi (309033) Kazem Behbehani (412126) Jehad Abubaker (437067) |
| dc.date.none.fl_str_mv | 2015-09-24T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/srep14448 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/DNAJB3_HSP-40_cochaperone_improves_insulin_signaling_and_enhances_glucose_uptake_in_vitro_through_JNK_repression/27045061 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Medical biochemistry and metabolomics Heat Shock Response (HSR) Insulin Resistance Type 2 Diabetes (T2D) DNAJB3 Obesity Inflammatory Markers Gene Expression |
| dc.title.none.fl_str_mv | DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Heat shock response (HSR) is an essential host-defense mechanism that is dysregulated in obesity-induced insulin resistance and type 2 diabetes (T2D). Our recent data demonstrated that DNAJB3 was downregulated in obese human subjects and showed negative correlation with inflammatory markers. Nevertheless, DNAJB3 expression pattern in diabetic subjects and its mode of action are not yet known. In this study, we showed reduction in DNAJB3 transcript and protein levels in PBMC and subcutaneous adipose tissue of obese T2D compared to obese non-diabetic subjects. Overexpression of DNAJB3 in HEK293 and 3T3-L1 cells reduced JNK, IRS-1 Ser-307 phosphorylation and enhanced Tyr-612 phosphorylation suggesting an improvement in IRS-1 signaling. Furthermore, DNAJB3 mediated the PI3K/AKT pathway activation through increasing AKT and AS160 phosphorylation. AS160 mediates the mobilization of GLUT4 transporter to the cell membrane and thereby improves glucose uptake. Using pre-adipocytes cells we showed that DNAJB3 overexpression caused a significant increase in the glucose uptake, possibly through its phosphorylation of AS160. In summary, our results shed the light on the possible role of DNAJB3 in improving insulin sensitivity and glucose uptake through JNK repression and suggest that DNAJB3 could be a potential target for therapeutic treatment of obesity-induced insulin resistance.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/srep14448" target="_blank">https://dx.doi.org/10.1038/srep14448</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_dc44099833889d3119e2edc532fbbeb2 |
| identifier_str_mv | 10.1038/srep14448 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/27045061 |
| publishDate | 2015 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repressionMohamed Abu-Farha (25322)Preethi Cherian (437070)Irina Al-Khairi (437069)Ali Tiss (437068)Abdelkrim Khadir (437074)Sina Kavalakatt (437073)Samia Warsame (437075)Mohammed Dehbi (309033)Kazem Behbehani (412126)Jehad Abubaker (437067)Biomedical and clinical sciencesMedical biochemistry and metabolomicsHeat Shock Response (HSR)Insulin ResistanceType 2 Diabetes (T2D)DNAJB3Obesity Inflammatory MarkersGene Expression<p dir="ltr">Heat shock response (HSR) is an essential host-defense mechanism that is dysregulated in obesity-induced insulin resistance and type 2 diabetes (T2D). Our recent data demonstrated that DNAJB3 was downregulated in obese human subjects and showed negative correlation with inflammatory markers. Nevertheless, DNAJB3 expression pattern in diabetic subjects and its mode of action are not yet known. In this study, we showed reduction in DNAJB3 transcript and protein levels in PBMC and subcutaneous adipose tissue of obese T2D compared to obese non-diabetic subjects. Overexpression of DNAJB3 in HEK293 and 3T3-L1 cells reduced JNK, IRS-1 Ser-307 phosphorylation and enhanced Tyr-612 phosphorylation suggesting an improvement in IRS-1 signaling. Furthermore, DNAJB3 mediated the PI3K/AKT pathway activation through increasing AKT and AS160 phosphorylation. AS160 mediates the mobilization of GLUT4 transporter to the cell membrane and thereby improves glucose uptake. Using pre-adipocytes cells we showed that DNAJB3 overexpression caused a significant increase in the glucose uptake, possibly through its phosphorylation of AS160. In summary, our results shed the light on the possible role of DNAJB3 in improving insulin sensitivity and glucose uptake through JNK repression and suggest that DNAJB3 could be a potential target for therapeutic treatment of obesity-induced insulin resistance.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/srep14448" target="_blank">https://dx.doi.org/10.1038/srep14448</a></p>2015-09-24T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/srep14448https://figshare.com/articles/journal_contribution/DNAJB3_HSP-40_cochaperone_improves_insulin_signaling_and_enhances_glucose_uptake_in_vitro_through_JNK_repression/27045061CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/270450612015-09-24T09:00:00Z |
| spellingShingle | DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression Mohamed Abu-Farha (25322) Biomedical and clinical sciences Medical biochemistry and metabolomics Heat Shock Response (HSR) Insulin Resistance Type 2 Diabetes (T2D) DNAJB3 Obesity Inflammatory Markers Gene Expression |
| status_str | publishedVersion |
| title | DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression |
| title_full | DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression |
| title_fullStr | DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression |
| title_full_unstemmed | DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression |
| title_short | DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression |
| title_sort | DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression |
| topic | Biomedical and clinical sciences Medical biochemistry and metabolomics Heat Shock Response (HSR) Insulin Resistance Type 2 Diabetes (T2D) DNAJB3 Obesity Inflammatory Markers Gene Expression |