Determining the role of arcuate nucleus glucokinase in the regulation of glucose homeostasis
确定弓状核葡萄糖激酶在葡萄糖稳态调节中的作用
基本信息
- 批准号:MR/N020472/1
- 负责人:
- 金额:$ 36.51万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Fellowship
- 财政年份:2016
- 资助国家:英国
- 起止时间:2016 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Diabetes affects 382 million people worldwide including 3.2 million people in the UK alone. Hence most people will know a friend or relative living with this condition. It is the commonest cause of end stage kidney failure and lower limb amputation and diabetics are 10-20 times more likely to go blind than those without diabetes. Management of diabetes costs the National Health Service a staggering 1 million pounds per hour. Sadly no cure has been found and, despite advancements in treatment, diabetes remains a major cause of disability and death. Diabetes is caused by the inability of the body to respond appropriately to high blood glucose (or sugar) levels. Historically, the pancreas, an organ which lies within the abdomen and produces the hormone insulin, was believed to be the main controller of glucose balance. Insulin is a hormone which lowers blood glucose levels. Most treatments to date have been directed at the level of the pancreas. However, there is increasing evidence that certain areas within the brain, particularly an area known as the arcuate nucleus, play a key role. Within the arcuate nucleus there is an increased concentration of glucokinase. Glucokinase is an enzyme which senses and breaks down glucose thereby preventing high glucose levels building up in the bloodstream and therefore preventing the development of diabetes. However, the specific function and mechanism of action of glucokinase within the arcuate nucleus itself is not known. I aim to determine the exact role and function of glucokinase within the arcuate nucleus of rats. Rats have very similar mechanisms of appetite and glucose control to humans and therefore provide excellent models for study. Within my laboratory at Imperial College, I have worked alongside experts in this field to collect pilot data in rat models to determine whether there is any scope in exploring this avenue further. My preliminary work is very promising and shows that increased activity of the glucokinase enzyme within the arcuate nucleus area of the brain improves blood sugar levels and hence should, in theory, protect against the development of diabetes. In understanding this novel pathway within the brain I aim to investigate this area further and establish if there are new undiscovered mechanisms within the brain (rather than pancreas alone) which are involved in blood sugar control and therefore development of diabetes. Once identified, these pathways may provide targets for more optimal treatment of diabetes.
糖尿病影响全球3.82亿人,其中仅英国就有320万人。因此,大多数人会认识一个朋友或亲戚生活在这种情况下。它是终末期肾衰竭和下肢截肢的最常见原因,糖尿病患者失明的可能性是非糖尿病患者的10-20倍。糖尿病的管理花费了国家卫生服务每小时惊人的100万英镑。可悲的是,没有找到治愈方法,尽管治疗取得了进展,糖尿病仍然是残疾和死亡的主要原因。糖尿病是由于身体无法对高血糖(或糖)水平做出适当反应而引起的。历史上,胰腺,一个位于腹部并产生胰岛素的器官,被认为是葡萄糖平衡的主要控制器。胰岛素是一种降低血糖水平的激素。迄今为止,大多数治疗都是针对胰腺水平的。然而,越来越多的证据表明,大脑中的某些区域,特别是被称为弓状核的区域,起着关键作用。在弓状核内,葡萄糖激酶的浓度增加。葡萄糖激酶是一种酶,它能感知和分解葡萄糖,从而防止血液中葡萄糖水平升高,从而防止糖尿病的发展。然而,弓状核内葡萄糖激酶本身的具体功能和作用机制尚不清楚。我的目的是确定葡萄糖激酶在大鼠弓状核的确切作用和功能。大鼠具有与人类非常相似的食欲和葡萄糖控制机制,因此为研究提供了极好的模型。在帝国理工学院的实验室里,我与该领域的专家一起收集了大鼠模型的试验数据,以确定是否有进一步探索这一途径的空间。我的初步工作是非常有希望的,并表明,增加活动的葡萄糖激酶在弓状核区域的大脑改善血糖水平,因此,在理论上,应该防止糖尿病的发展。在了解大脑中的这种新途径时,我的目标是进一步研究这一领域,并确定大脑(而不仅仅是胰腺)中是否存在新的未发现的机制,这些机制参与血糖控制,从而发展为糖尿病。一旦确定,这些途径可能为糖尿病的更佳治疗提供目标。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Ligand-Specific Factors Influencing GLP-1 Receptor Post-Endocytic Trafficking and Degradation in Pancreatic Beta Cells.
- DOI:10.3390/ijms21218404
- 发表时间:2020-11-09
- 期刊:
- 影响因子:5.6
- 作者:Fang Z;Chen S;Manchanda Y;Bitsi S;Pickford P;David A;Shchepinova MM;Corrêa IR Jr;Hodson DJ;Broichhagen J;Tate EW;Reimann F;Salem V;Rutter GA;Tan T;Bloom SR;Tomas A;Jones B
- 通讯作者:Jones B
Reply: Clinical trial registry alone is not adequate: on the perception of possible endpoint switching and P-hacking.
答复:仅凭临床试验注册是不够的:对可能的终点切换和 P-hacking 的看法。
- DOI:10.1093/humrep/dex360
- 发表时间:2018
- 期刊:
- 影响因子:0
- 作者:Abbara A
- 通讯作者:Abbara A
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Risheka Ratnasabapathy其他文献
Risheka Ratnasabapathy的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似国自然基金
PfAP2-R介导的PfCRT转录调控在恶性疟原虫对喹啉类药物抗性中的作用及机制研究
- 批准号:82372275
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
Sestrin2抑制内质网应激对早产儿视网膜病变的调控作用及其机制研究
- 批准号:82371070
- 批准年份:2023
- 资助金额:49.00 万元
- 项目类别:面上项目
相似海外基金
Regulation of binge-like ethanol intake by arcuate POMC projection neurons
弓形 POMC 投射神经元对暴饮暴食乙醇摄入的调节
- 批准号:
10594822 - 财政年份:2023
- 资助金额:
$ 36.51万 - 项目类别:
Roles of MLL4-complex in development of hypothalamic arcuate neurons
MLL4复合物在下丘脑弓状神经元发育中的作用
- 批准号:
9900089 - 财政年份:2019
- 资助金额:
$ 36.51万 - 项目类别:
Glutamatergic Neurons in the Arcuate Nucleus (ARC) and Regulation of Satiety
弓状核 (ARC) 中的谷氨酸能神经元与饱腹感的调节
- 批准号:
9353418 - 财政年份:2016
- 资助金额:
$ 36.51万 - 项目类别:
Timing, Lineage, and Mechanism Underlying Development of Arcuate Nucleus Neurons
弓状核神经元发育的时间、谱系和机制
- 批准号:
9326289 - 财政年份:2015
- 资助金额:
$ 36.51万 - 项目类别:
The role of neurpopeptide Y in the arcuate nucleus of the hypothalamus in the regulation of energy expenditure and the involvment of its peripherally expressed receptor type-1 in the regulation of energy homeostasis in mice
下丘脑弓状核神经肽Y在能量消耗调节中的作用及其外周表达的1型受体在小鼠能量稳态调节中的作用
- 批准号:
231922378 - 财政年份:2012
- 资助金额:
$ 36.51万 - 项目类别:
Research Fellowships
Arcuate nucleus glutamatergic neurons modulate energy homeostasis
弓状核谷氨酸能神经元调节能量稳态
- 批准号:
8058707 - 财政年份:2010
- 资助金额:
$ 36.51万 - 项目类别:
Arcuate nucleus glutamatergic neurons modulate energy homeostasis
弓状核谷氨酸能神经元调节能量稳态
- 批准号:
8235967 - 财政年份:2010
- 资助金额:
$ 36.51万 - 项目类别:
Arcuate Nucleus Glutamatergic Neurons Modulate Energy Homeostasis
弓状核谷氨酸神经元调节能量稳态
- 批准号:
8423379 - 财政年份:2010
- 资助金额:
$ 36.51万 - 项目类别:
Arcuate nucleus glutamatergic neurons modulate energy homeostasis
弓状核谷氨酸能神经元调节能量稳态
- 批准号:
7889376 - 财政年份:2010
- 资助金额:
$ 36.51万 - 项目类别:
The Arcuate Nucleus: A Genetic Assessment of Function
弓状核:功能的遗传评估
- 批准号:
7392810 - 财政年份:2007
- 资助金额:
$ 36.51万 - 项目类别: