Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis
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Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis. / Ma, Yue; Ratnasabapathy, Risheka; Izzi-Engbeaya, Chioma; Nguyen-Tu, Marie-Sophie; Richardson, Errol; Hussain, Sufyan; De Backer, Ivan; Holton, Christopher; Norton, Mariana; Carrat, Gaelle; Schwappach, Blanche; Rutter, Guy A; Dhillo, Waljit S; Gardiner, James.
In: DIABETES OBES METAB, Vol. 20, No. 9, 09.2018, p. 2246-2254.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis
AU - Ma, Yue
AU - Ratnasabapathy, Risheka
AU - Izzi-Engbeaya, Chioma
AU - Nguyen-Tu, Marie-Sophie
AU - Richardson, Errol
AU - Hussain, Sufyan
AU - De Backer, Ivan
AU - Holton, Christopher
AU - Norton, Mariana
AU - Carrat, Gaelle
AU - Schwappach, Blanche
AU - Rutter, Guy A
AU - Dhillo, Waljit S
AU - Gardiner, James
N1 - © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
KW - Animals
KW - Arcuate Nucleus of Hypothalamus/enzymology
KW - Diabetes Mellitus, Experimental/blood
KW - Diabetes Mellitus, Type 2/blood
KW - Glucokinase/metabolism
KW - Glucose/metabolism
KW - Glucose Tolerance Test
KW - Homeostasis/physiology
KW - Insulin Secretion/physiology
KW - Male
KW - Rats
KW - Rats, Wistar
KW - Rats, Zucker
U2 - 10.1111/dom.13359
DO - 10.1111/dom.13359
M3 - SCORING: Journal article
C2 - 29748994
VL - 20
SP - 2246
EP - 2254
JO - DIABETES OBES METAB
JF - DIABETES OBES METAB
SN - 1462-8902
IS - 9
ER -