DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression

Mohamed Abu-Farha, Preethi Cherian, Irina Al-Khairi, Ali Tiss, Abdelkrim Khadir, Sina Kavalakatt, Samia Warsame, Mohammed Dehbi, Kazem Behbehani, Jehad Abubaker

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number14448
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 24 Sep 2015

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Phosphorylation
Insulin
Insulin Resistance
Glucose
Type 2 Diabetes Mellitus
Obesity
3T3-L1 Cells
Heat-Shock Response
Subcutaneous Fat
Phosphatidylinositol 3-Kinases
Adipocytes
Down-Regulation
Cell Membrane
In Vitro Techniques
Proteins
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Abu-Farha, M., Cherian, P., Al-Khairi, I., Tiss, A., Khadir, A., Kavalakatt, S., ... Abubaker, J. (2015). DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression. Scientific Reports, 5, [14448]. https://doi.org/10.1038/srep14448

DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression. / Abu-Farha, Mohamed; Cherian, Preethi; Al-Khairi, Irina; Tiss, Ali; Khadir, Abdelkrim; Kavalakatt, Sina; Warsame, Samia; Dehbi, Mohammed; Behbehani, Kazem; Abubaker, Jehad.

In: Scientific Reports, Vol. 5, 14448, 24.09.2015.

Research output: Contribution to journalArticle

Abu-Farha, M, Cherian, P, Al-Khairi, I, Tiss, A, Khadir, A, Kavalakatt, S, Warsame, S, Dehbi, M, Behbehani, K & Abubaker, J 2015, 'DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression', Scientific Reports, vol. 5, 14448. https://doi.org/10.1038/srep14448
Abu-Farha, Mohamed ; Cherian, Preethi ; Al-Khairi, Irina ; Tiss, Ali ; Khadir, Abdelkrim ; Kavalakatt, Sina ; Warsame, Samia ; Dehbi, Mohammed ; Behbehani, Kazem ; Abubaker, Jehad. / DNAJB3/HSP-40 cochaperone improves insulin signaling and enhances glucose uptake in vitro through JNK repression. In: Scientific Reports. 2015 ; Vol. 5.
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