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

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• 作者：Mark J. W. Hanssen ; Roel Wierts ; Joris Hoeks ; Anne Gemmink ; Boudewijn Brans…
• 关键词：Brown adipose tissue ; Insulin resistance
• 刊名：Diabetologia
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：58
• 期：3
• 页码：586-595
• 全文大小：576 KB
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• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Internal Medicine
  Metabolic Diseases
  Human Physiology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0428

文摘

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).