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 journalSCORING: Journal articleResearchpeer-review

Harvard

Ma, Y, Ratnasabapathy, R, Izzi-Engbeaya, C, Nguyen-Tu, M-S, Richardson, E, Hussain, S, De Backer, I, Holton, C, Norton, M, Carrat, G, Schwappach, B, Rutter, GA, Dhillo, WS & Gardiner, J 2018, 'Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis', DIABETES OBES METAB, vol. 20, no. 9, pp. 2246-2254. https://doi.org/10.1111/dom.13359

APA

Ma, Y., Ratnasabapathy, R., Izzi-Engbeaya, C., Nguyen-Tu, M-S., Richardson, E., Hussain, S., De Backer, I., Holton, C., Norton, M., Carrat, G., Schwappach, B., Rutter, G. A., Dhillo, W. S., & Gardiner, J. (2018). Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis. DIABETES OBES METAB, 20(9), 2246-2254. https://doi.org/10.1111/dom.13359

Vancouver

Ma Y, Ratnasabapathy R, Izzi-Engbeaya C, Nguyen-Tu M-S, Richardson E, Hussain S et al. Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis. DIABETES OBES METAB. 2018 Sep;20(9):2246-2254. https://doi.org/10.1111/dom.13359

Bibtex

@article{cbc72c698443447d82acbacff96bfcb1,
title = "Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis",
abstract = "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.",
keywords = "Animals, Arcuate Nucleus of Hypothalamus/enzymology, Diabetes Mellitus, Experimental/blood, Diabetes Mellitus, Type 2/blood, Glucokinase/metabolism, Glucose/metabolism, Glucose Tolerance Test, Homeostasis/physiology, Insulin Secretion/physiology, Male, Rats, Rats, Wistar, Rats, Zucker",
author = "Yue Ma and Risheka Ratnasabapathy and Chioma Izzi-Engbeaya and Marie-Sophie Nguyen-Tu and Errol Richardson and Sufyan Hussain and {De Backer}, Ivan and Christopher Holton and Mariana Norton and Gaelle Carrat and Blanche Schwappach and Rutter, {Guy A} and Dhillo, {Waljit S} and James Gardiner",
note = "{\textcopyright} 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.",
year = "2018",
month = sep,
doi = "10.1111/dom.13359",
language = "English",
volume = "20",
pages = "2246--2254",
journal = "DIABETES OBES METAB",
issn = "1462-8902",
publisher = "Wiley-Blackwell",
number = "9",

}

RIS

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 -