Extra-nuclear telomerase reverse transcriptase (TERT) regulates glucose transport in skeletal muscle cells

Fozia Shaheen, Dimitris K. Grammatopoulos*, Jürgen Müller, Victor A. Zammit, Hendrik Lehnert

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Telomerase reverse transcriptase (TERT) is a key component of the telomerase complex. By lengthening telomeres in DNA strands, TERT increases senescent cell lifespan. Mice that lack TERT age much faster and exhibit age-related conditions such as osteoporosis, diabetes and neurodegeneration. Accelerated telomere shortening in both human and animal models has been documented in conditions associated with insulin resistance, including T2DM. We investigated the role of TERT, in regulating cellular glucose utilisation by using the myoblastoma cell line C2C12, as well as primary mouse and human skeletal muscle cells. Inhibition of TERT expression or activity by using siRNA (100. nM) or specific inhibitors (100. nM) reduced basal 2-deoxyglucose uptake by ~. 50%, in all cell types, without altering insulin responsiveness. In contrast, TERT over-expression increased glucose uptake by 3.25-fold. In C2C12 cells TERT protein was mostly localised intracellularly and stimulation of cells with insulin induced translocation to the plasma membrane. Furthermore, co-immunoprecipitation experiments in C2C12 cells showed that TERT was constitutively associated with glucose transporters (GLUTs) 1, 4 and 12 via an insulin insensitive interaction that also did not require intact PI3-K and mTOR pathways. Collectively, these findings identified a novel extra-nuclear function of TERT that regulates an insulin-insensitive pathway involved in glucose uptake in human and mouse skeletal muscle cells.

Original languageEnglish
Pages (from-to)1762-1769
Number of pages8
JournalBBA : Molecular Basis of Disease
Volume1842
Issue number9
Early online date23 Jun 2014
DOIs
Publication statusPublished - Sep 2014

Fingerprint

Telomerase
Muscle Cells
Skeletal Muscle
Glucose
Insulin
Muscle Tissue Neoplasms
Telomere Homeostasis
Telomere Shortening
Facilitative Glucose Transport Proteins
Deoxyglucose
Immunoprecipitation
Small Interfering RNA
Osteoporosis
Insulin Resistance
Animal Models
Cell Membrane
Cell Line
DNA

Bibliographical note

© 2014, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • ageing
  • diabetes
  • glucose transporter
  • insulin
  • muscle
  • TERT

Cite this

Shaheen, Fozia ; Grammatopoulos, Dimitris K. ; Müller, Jürgen ; Zammit, Victor A. ; Lehnert, Hendrik. / Extra-nuclear telomerase reverse transcriptase (TERT) regulates glucose transport in skeletal muscle cells. In: BBA : Molecular Basis of Disease. 2014 ; Vol. 1842, No. 9. pp. 1762-1769.
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Extra-nuclear telomerase reverse transcriptase (TERT) regulates glucose transport in skeletal muscle cells. / Shaheen, Fozia; Grammatopoulos, Dimitris K.; Müller, Jürgen; Zammit, Victor A.; Lehnert, Hendrik.

In: BBA : Molecular Basis of Disease, Vol. 1842, No. 9, 09.2014, p. 1762-1769.

Research output: Contribution to journalArticle

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AU - Grammatopoulos, Dimitris K.

AU - Müller, Jürgen

AU - Zammit, Victor A.

AU - Lehnert, Hendrik

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