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Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis
Author(s) -
Ma Yue,
Ratnasabapathy Risheka,
IzziEngbeaya Chioma,
NguyenTu MarieSophie,
Richardson Errol,
Hussain Sufyan,
De Backer Ivan,
Holton Christopher,
Norton Mariana,
Carrat Gaelle,
Schwappach Blanche,
Rutter Guy A.,
Dhillo Waljit S.,
Gardiner James
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13359
Subject(s) - glucokinase , medicine , endocrinology , glucose homeostasis , arcuate nucleus , arc (geometry) , insulin , chemistry , homeostasis , secretion , hypothalamus , biology , insulin resistance , geometry , mathematics
Aims To investigate the role of arcuate glucokinase (GK) in the regulation of glucose homeostasis. Materials and methods A recombinant adeno‐associated virus expressing either GK or an antisense GK construct was used to alter GK activity specifically in the hypothalamic arcuate nucleus (arc). GK activity in this nucleus was also increased by stereotactic injection of the GK activator, compound A. The effect of altered arc GK activity on glucose homeostasis was subsequently investigated using glucose and insulin tolerance tests. Results. Increased GK activity specifically within the arc increased insulin secretion and improved glucose tolerance in rats during oral glucose tolerance tests. Decreased GK activity in this nucleus reduced insulin secretion and increased glucose levels during the same tests. Insulin sensitivity was not affected in either case. The effect of arc GK was maintained in a model of type 2 diabetes. Conclusions These results demonstrate a role for arc GK in systemic glucose homeostasis.