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
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