TMF1 is upregulated by insulin and is required for a sustained glucose homeostasis.


Journal

FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484

Informations de publication

Date de publication:
02 2021
Historique:
received: 06 09 2020
revised: 20 11 2020
accepted: 07 12 2020
entrez: 21 1 2021
pubmed: 22 1 2021
medline: 16 7 2021
Statut: ppublish

Résumé

Insulin-regulated glucose homeostasis is a critical and intricate physiological process, of which not all regulatory components have been deciphered. One of the key players in modulating glucose uptake by cells is the glucose transporter-GLUT4. In this study, we aimed to explore the regulatory role of the trans-Golgi-associated protein-TATA Element Modulatory Factor (TMF1) in the GLUT4 mediated, insulin-directed glucose uptake. By establishing and using TMF1-/- myoblasts and mice, we examined the effect of TMF1 absence on the insulin driven functioning of GLUT4. We show that TMF1 is upregulated by insulin in myoblasts, and is essential for the formation of insulin responsive, glucose transporter GLUT4-containing vesicles. Absence of TMF1 leads to the retention of GLUT4 in perinuclear compartments, and to severe impairment of insulin-stimulated GLUT4 trafficking throughout the cytoplasm and to the cell plasma membrane. Accordingly, glucose uptake is impaired in TMF1-/- cells, and TMF1-/- mice are hyperglycemic. This is reflected by the mice impaired blood glucose clearance and increased blood glucose level. Correspondingly, TMF1-/- animals are leaner than their normal littermates. Thus, TMF1 is a novel effector of insulin-regulated glucose homeostasis, and dys-functioning of this protein may contribute to the onset of a diabetes-like disorder.

Identifiants

pubmed: 33475194
doi: 10.1096/fj.202001995R
doi:

Substances chimiques

Blood Glucose 0
DNA-Binding Proteins 0
Insulin 0
Tmf1 protein, mouse 0
Transcription Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e21295

Informations de copyright

© 2021 Federation of American Societies for Experimental Biology.

Références

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Auteurs

Roni Rahimi (R)

The Mina and Everard Goodman Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel.

Israel Malek (I)

The Mina and Everard Goodman Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel.

Tali Lerrer-Goldshtein (T)

The Mina and Everard Goodman Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel.

Yoav Elkis (Y)

The Mina and Everard Goodman Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel.

Irit Shoval (I)

The Mina and Everard Goodman Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel.

Avi Jacob (A)

The Mina and Everard Goodman Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel.

Sally Shpungin (S)

The Mina and Everard Goodman Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel.

Uri Nir (U)

The Mina and Everard Goodman Faculty of Life-Sciences, Bar-Ilan University, Ramat-Gan, Israel.

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Classifications MeSH