Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis

被引：11
|
作者：
Ma, Yue [1 ]
Ratnasabapathy, Risheka [1 ]
Izzi-Engbeaya, Chioma [1 ]
Nguyen-Tu, Marie-Sophie [2 ]
Richardson, Errol [1 ]
Hussain, Sufyan [1 ]
De Backer, Ivan [1 ]
Holton, Christopher [1 ]
Norton, Mariana [1 ]
Carrat, Gaelle [2 ]
Schwappach, Blanche [3 ]
Rutter, Guy A. [2 ]
Dhillo, Waljit S. [1 ]
Gardiner, James [1 ]
机构：
[1] Imperial Coll London, Div Diabet Endocrinol & Metab, Sect Endocrinol & Invest Med, London, England
[2] Imperial Coll London, Div Diabet Endocrinol & Metab, Sect Cell Biol & Funct Genom, London, England
[3] Univ Med Gottingen, Heart Res Ctr Gottingen, Ctr Biochem & Mol Cell Biol, Dept Mol Biol, Gottingen, Germany
来源：
DIABETES OBESITY & METABOLISM | 2018年 / 20卷 / 09期
基金：
英国惠康基金; 英国医学研究理事会;
关键词：
glucokinase activator; glycaemic control; neuropharmacology; pharmacogenetics; BETA-CELL GLUCOKINASE; RAT-BRAIN; EXPRESSING NEURONS; PANCREATIC-ISLET; TRANSGENIC MICE; GENE-TRANSFER; LIVER; LOCALIZATION; HYPOGLYCEMIA; HYPERPHAGIA;
D O I：
10.1111/dom.13359
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
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.
引用
收藏
页码：2246 / 2254
页数：9
相关论文
共 50 条
  • [21] The Hypothalamic Arcuate Nucleus Dopaminergic Neurons: More Than Just Prolactin Secretion
    Lim, Luis Wei Cheng
    Egnot, Christopher Thomas
    Papaioannou, Panagiotis
    Yip, Siew Hoong
    ENDOCRINOLOGY, 2025, 166 (03)
  • [22] Hypothalamic arcuate nucleus tyrosine hydroxylase neurons play orexigenic role in energy homeostasis
    Zhang, Xiaobing
    van den Pol, Anthony N.
    NATURE NEUROSCIENCE, 2016, 19 (10) : 1341 - +
  • [23] Hypothalamic arcuate nucleus tyrosine hydroxylase neurons play orexigenic role in energy homeostasis
    Xiaobing Zhang
    Anthony N van den Pol
    Nature Neuroscience, 2016, 19 : 1341 - 1347
  • [24] Hypothalamic Insulin Resistance in Obesity: Effects on Glucose Homeostasis
    Chen, Weiyi
    Balland, Eglantine
    Cowley, Michael A.
    NEUROENDOCRINOLOGY, 2017, 104 (04) : 364 - 381
  • [25] Bone Regulation of Insulin Secretion and Glucose Homeostasis
    Ducy, Patricia
    ENDOCRINOLOGY, 2020, 161 (10)
  • [26] Different effects of insulin on electrically distinct hypothalamic arcuate nucleus (ARC) neurones
    Burdakov, D
    Ashcroft, FM
    BIOPHYSICAL JOURNAL, 2002, 82 (01) : 626A - 626A
  • [27] Electrophysiological characterization of glucose sensing neurons in the hypothalamic arcuate nucleus of male rats
    Garduno, Julieta
    Hernandez-Lopez, Salvador
    Castillo Rolon, Diego
    de la Cruz, Lizbeth
    Hernandez-Vazquez, Fabiola
    Reyes-Vaca, Arturo
    Arenas, Isabel
    Bravo-Martinez, Jorge
    Garcia, David E.
    NEUROSCIENCE LETTERS, 2019, 703 : 168 - 176
  • [28] Sex Differences in Acclimation of Hypothalamic Arcuate Glucokinase Gene and Protein Expression to Repeated Intermediate Insulin Administration
    Nedungadi, T. Prashant
    Genabai, Naresh K.
    Parihar, Manish
    Briski, Karen P.
    NEUROENDOCRINOLOGY, 2009, 89 (04) : 377 - 386
  • [29] Kisspeptin Signalling in the Hypothalamic Arcuate Nucleus Regulates GnRH Pulse Generator Frequency in the Rat
    Li, Xiao-Feng
    Kinsey-Jones, James S.
    Cheng, Yewsong
    Knox, Alice M. I.
    Lin, Yuanshao
    Petrou, Nikoletta A.
    Roseweir, Antonia
    Lightman, Stafford L.
    Milligan, Stuart R.
    Millar, Robert P.
    O'Byrne, Kevin T.
    PLOS ONE, 2009, 4 (12):
  • [30] Glucose Transporter-1 in the Hypothalamic Glial Cells Regulates Glucose Homeostasis
    Yang, Clair S.
    Mighiu, Patricia
    Chari, Madhu
    Lam, Carol K. L.
    Lam, Tony K. T.
    DIABETES, 2011, 60 : A463 - A463
12345