Glucokinase is a member of the hexokinase family of enzymes. However, its main function is not in the production of cellular energy but to act as part of the glucose sensing mechanism of cells. Glucokinase is widely expressed in the brain including within the hypothalamus and functions as part of the glucose sensing mechanism in an analogous manner to is role in the pancreatic β-cells [1-2]. Within the hypothalamus glucokinase is expressed in several nuclei including the arcuate nucleus and the ventromedial nucleus (VMN). In the VMN glucokinase has an important role in the regulation of the counter regulatory response [3-4]. Until recently its role in the in the arcuate nucleus was less well characterised. We have recently characterised the role of arcuate nucleus glucokinase using recombinant adeno-associated virus to both increase and decrease glucokinase activity specifically in the arcuate nucleus. In addition we have used pharmacological agents to increase glucokinase activity in the arcuate and also alter activity of KATP . We found that glucokinase within the arcuate nucleus has important roles in the regulation of both energy [5] and glucose homeostasis [6]. Arcuate nucleus glucokinase regulates food intake and this effect is specific for glucose with intake of others sugars unaffected. This effect is mediated via the KATP and voltage sensitive calcium channels. Arcuate nucleus glucokinase also regulates glucose stimulated insulin release and this effect is mediated via the KATP. Importantly this response is maintained in a model of type 2 diabetes suggesting targeting this effect could be a therapeutic approach to treating this disease. Together these finding suggest that arcuate nucleus glucokinase acts to stimulate intake of glucose rich foods and then ensure that this glucose will be efficiently utilised and store.
Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, SA028
Research Symposium: The role of glucose sensing by glucokinase in the arcuate nucleus in the regulation of energy and glucose homeostasis
J. Gardiner1
1. Imperial College London, London, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.