Regulation by glucose and insulin of the neurons in feeding-regulatory centers and its alteration in obesity and diabetes
葡萄糖和胰岛素对摄食调节中心神经元的调节及其在肥胖和糖尿病中的改变
基本信息
- 批准号:12470231
- 负责人:
- 金额:$ 8.45万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2000
- 资助国家:日本
- 起止时间:2000 至 2002
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
AIM : This study aimed to clarify the effects of important feeding-controlling substances of the visceral origin, such as glucose, insulin, leptin and ghrelin, on the neurons in the hypothalamic feeding-regulatory centers, which include neuropeptide Y (NPY), proopiomelanocortin (POMC) and orexin neurons.METHODS : Single neurons were isolated from the hypothalamus of rats aged 6-8 weeks. The responses of the single neurons to substances were assessed by measurements of cytosolic Ca^<2+> concentration and ion channel currents, followed by immunocytochemical identification of the neuron species. In addition, in vivo feeding experiments and histological methods were used.RESULTS:1.Orexin neurons in the lateral hypothalamus were activated by lowering glucose concentrations, providing a mechanism how orexin neurons are regulated. In addition to its feeding effect, we found that orexin activates dopamine neurons in the ventral tegmental area and thereby stimulates emotional behavior such as hyperlocomotion and stereotypy.2.NPY neurons in the arcuate nucleus (ARC), which are implicated in stimulation of feeding, were activated by lowering glucose concentrations, orexin and ghrelin, while they were inhibited by elevating glucose concentrations, leptin and insulin.3.POMC neurons in the ARC and glucose-responsive neurons in the ventromedial hypothalamus (VMH), both implicated in inhibition of feeding, were activated by elevating glucose concentrations, leptin and insulin, while they were inhibited by lowering glucose concentrations and orexin.4.Orexin type 1 and 2 receptors were linked to distinct signal transduction mechanisms and coupled to activation of NPY neurons and inhibition of POMC neurons, respectively.5.NPY neurons and POMC neurons in the ARC are the direct targets of principal visceral and neural substances that affect feeding and thereby serve as the integration centers.
目的:本研究旨在探讨内脏源性重要摄食控制物质葡萄糖、胰岛素、瘦素和ghrelin对下丘脑摄食调节中枢神经元神经肽Y(neuropeptide Y,NPY)、阿黑皮素原(proopiomelanocortin,POMC)和食欲素(orexin)的影响。通过测量胞浆Ca^2+浓度和离子通道电流来评估单个神经元对物质的反应,然后通过免疫细胞化学鉴定神经元的种类。结果:1.降低葡萄糖浓度可激活下丘脑外侧区食欲素神经元,为食欲素神经元的调节提供了机制。除摄食作用外,我们还发现食欲素还能激活腹侧被盖区的多巴胺神经元,从而刺激情绪行为,如过度运动和刻板行为。2.弓状核(ARC)中与摄食刺激有关的NPY神经元被葡萄糖浓度降低、食欲素和ghrelin激活,而葡萄糖浓度升高则抑制它们。3. ARC中的POMC神经元和腹内侧下丘脑(VMH)中的葡萄糖反应神经元,两者都涉及摄食抑制,通过升高葡萄糖浓度、瘦素和胰岛素而被激活,而降低葡萄糖浓度和食欲素则可抑制食欲素1型和2型受体与不同的信号转导有关5. ARC中的NPY神经元和POMC神经元是影响摄食的主要内脏和神经物质的直接靶点,从而充当整合中心。
项目成果
期刊论文数量(92)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Muroya S: "Lowering glucose concentrations increases cytosolic Ca^<2+> in orexin neurons of the rat lateral hypothalamus"Neurosci. Lett. 309. 165-168 (2001)
Muroya S:“降低葡萄糖浓度会增加大鼠下丘脑外侧食欲素神经元中的胞质Ca 2+ ”Neurosci。
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- 影响因子:0
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- 通讯作者:
Kakei M., Yada T., Nakagawa A., Nakabayashi H.: "Glucagon-like peptide-1 evokes action potentials and increases cytosolic Ca^<2+> in rat nodose ganglion neurons"Auton.Neurosci.. 102. 39-44 (2002)
Kakei M.、Yada T.、Nakakawa A.、Nakabayashi H.:“胰高血糖素样肽-1 诱发动作电位并增加大鼠结状神经节神经元中的胞质 Ca^<2>”Auton.Neurosci.. 102. 39-44
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Nakata M, Yada T.: "Endocrinology : Nitric Oxide-mediated insulin secretion in response to citrulline in islet β-cells"Pancreas. 27. 209-213 (2003)
Nakata M,Yada T.:“内分泌学:胰岛 β 细胞中一氧化氮介导的胰岛素分泌对瓜氨酸的反应”胰腺。 27. 209-213 (2003)
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Zhu L., Onaka T., Yada T.: "Activation of orexin neurons after noxious but not conditioned fear stimuli in rats"Neuroreport. 19. 1351-1353 (2002)
Zhu L.、Onaka T.、Yada T.:“大鼠受到有害但非条件性恐惧刺激后食欲素神经元的激活”Neuroreport。
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- 影响因子:0
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Uramura K: "Orexin-A Activates Phospholipase C-and Protein Kinase C-Mediated Ca^<2+> Signaling in Dopamine Neurons of the Ventral Tegmental Area"NeuroReport. 12. 1885-1889 (2001)
Uramura K:“Orexin-A 激活磷脂酶 C 和蛋白激酶 C 介导的 Ca^<2 > 腹侧被盖区多巴胺神经元中的信号传导”NeuroReport。
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YADA Toshihiko其他文献
YADA Toshihiko的其他文献
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{{ truncateString('YADA Toshihiko', 18)}}的其他基金
Central and organ mechanisms for anti-obesity/diabetes effects of rare sugar allulose
稀有糖阿洛酮糖抗肥胖/糖尿病作用的中枢和器官机制
- 批准号:
19H04045 - 财政年份:2019
- 资助金额:
$ 8.45万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
GLP-1 and insulin synergize to activate vagal afferent nerves leading to central regulation of metabolism, feeding and blood pressure
GLP-1 和胰岛素协同激活迷走神经传入神经,从而实现代谢、进食和血压的中枢调节
- 批准号:
26670453 - 财政年份:2014
- 资助金额:
$ 8.45万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Regulation by Na-K pump of glucose-sensitive NPY neurons and feeding behavior, and its dysfunction in hyperphagia and obesity
Na-K泵对葡萄糖敏感的NPY神经元和摄食行为的调节及其在食欲过多和肥胖中的功能障碍
- 批准号:
24659101 - 财政年份:2012
- 资助金额:
$ 8.45万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Novel function of oxytocin : its anorectic neuronal pathway and(patho) physiological role in regulating feeding
催产素的新功能:其厌食神经元通路和调节摄食的(病理)生理作用
- 批准号:
22659044 - 财政年份:2010
- 资助金额:
$ 8.45万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Ghrelin : its status as a pancreatic hormone, mechanisms by which it regulates insulin release and glucose metabolism, and its application for treating diabetes.
生长素释放肽:其作为胰腺激素的地位、其调节胰岛素释放和葡萄糖代谢的机制及其在治疗糖尿病中的应用。
- 批准号:
20390061 - 财政年份:2008
- 资助金额:
$ 8.45万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Inputs and outputs of NPY and BDNF neurons in the hypothalamus and their implication in feeding and metabolic regulation
下丘脑 NPY 和 BDNF 神经元的输入和输出及其在摄食和代谢调节中的意义
- 批准号:
18390065 - 财政年份:2006
- 资助金额:
$ 8.45万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Regulation by endogenous ghrelin of insulin release, feeding and glucose metabolism
内源性生长素释放肽对胰岛素释放、摄食和葡萄糖代谢的调节
- 批准号:
16390053 - 财政年份:2004
- 资助金额:
$ 8.45万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Novel signaling function of adipocytes
脂肪细胞的新信号传导功能
- 批准号:
15081211 - 财政年份:2003
- 资助金额:
$ 8.45万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
Control of glucose metabolism by PACAP : stimulation of insulin secretion and potentiation of insulin action
PACAP 控制葡萄糖代谢:刺激胰岛素分泌并增强胰岛素作用
- 批准号:
09670052 - 财政年份:1997
- 资助金额:
$ 8.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Extraordinarily Potent Insulinotropin PACAP : Its Characterization as a Pancreatic Peptide and Action Mechanisms in Islet beta-Cells
极其有效的促胰岛素素 PACAP:其作为胰肽的特性及其在胰岛 β 细胞中的作用机制
- 批准号:
06454147 - 财政年份:1994
- 资助金额:
$ 8.45万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
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确定弓状核葡萄糖激酶在葡萄糖稳态调节中的作用
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