The impact of ageing, fasting and high-fat diet on central and peripheral glucose tolerance and glucose-sensing neural networks in the arcuate nucleus

M. van den Top, F.-Y. Zhao, R. Viriyapong, N. J. Michael, A. C. Munder, J. T. Pryor, L. P. Renaud, D. Spanswick

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Obesity and ageing are risk factors for diabetes. In the present study, we investigated the effects of ageing, obesity and fasting on central and peripheral glucose tolerance and on glucose-sensing neuronal function in the arcuate nucleus of rats, with a view to providing insight into the central mechanisms regulating glucose homeostasis and how they change or are subject to dysfunction with ageing and obesity. We show that, following a glucose load, central glucose tolerance at the level of the cerebrospinal fluid (CSF) and plasma is significantly reduced in rats maintained on a high-fat diet (HFD). With ageing, up to 2 years, central glucose tolerance was impaired in an age-dependent manner, whereas peripheral glucose tolerance remained unaffected. Ageing-induced peripheral glucose intolerance was improved by a 24-hour fast, whereas central glucose tolerance was not corrected. Pre-wean, immature animals have elevated basal plasma glucose levels and a delayed increase in central glucose levels following peripheral glucose injection compared to mature animals. Electrophysiological recording techniques revealed an energy-status-dependent role for glucose-excited, inhibited and adapting neurones, along with glucose-induced changes in synaptic transmission. We conclude that ageing affects central glucose tolerance, whereas HFD profoundly affects central and peripheral glucose tolerance and, in addition, glucose-sensing neurones adapt function in an energy-status-dependent manner.

Original languageEnglish
Article numbere12528
Number of pages23
JournalJournal of Neuroendocrinology
Issue number10
Publication statusPublished - 1 Oct 2017


  • arcuate nucleus
  • electrophysiology
  • glucose
  • glucose tolerance
  • hypothalamus
  • POMC

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