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Erschienen in:

01.03.2015 | Article

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

verfasst von: Mark J. W. Hanssen, Roel Wierts, Joris Hoeks, Anne Gemmink, Boudewijn Brans, Felix M. Mottaghy, Patrick Schrauwen, Wouter D. van Marken Lichtenbelt

Erschienen in: Diabetologia | Ausgabe 3/2015

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Abstract

Aims/hypothesis

Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation—at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain.

Methods

We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[¹⁸F]fluoro-d-glucose positron emission tomography/computed tomography ([¹⁸F]FDG-PET/CT) imaging.

Results

We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans.

Conclusions/interpretation

Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions.

Trial registration: www.trialregister.nl NTR3523

Funding: This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373 to WDvML) and by the Netherlands Organization for Scientific Research (TOP 91209037 to WDvML).

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Titel: Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance
verfasst von: Mark J. W. Hanssen
Roel Wierts
Joris Hoeks
Anne Gemmink
Boudewijn Brans
Felix M. Mottaghy
Patrick Schrauwen
Wouter D. van Marken Lichtenbelt
Publikationsdatum: 01.03.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 3/2015
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-014-3465-8

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