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
• 负责人: YADA Toshihiko
• 金额: $ 8.96万
• 依托单位: JICHI MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390053/
• 关键词: ghrelin; insulin release; β-cells; cytosolic Ca^<2+>; plasma glucose; feeding center; NPY neuron; leptin; カルシウム; Kチャネル; 膵灌流; Ca; 膵島; NPY; 摂食; 弓状核

In this study, ghrelin and its receptor, growth hormone (GH) secretagogue-receptor (GHS-R), were expressed in the pancreatic islets. Counteraction of endogenous ghrelin by intraperitoneal injection of specific GHS-R antagonists markedly lowered fasting glucose concentrations, attenuated plasma glucose elevation and enhanced insulin responses during glucose tolerance test (GTT). Conversely, intraperitoneal exogenous ghrelin elevated fasting glucose concentrations, enhanced plasma glucose elevation and attenuated insulin responses during GTT. In perfused rat pancreas that retains intact circulation, GHS-R blockade and antiserum against ghrelin enhanced glucose-induced insulin release, while exogenous ghrelin suppressed it. In isolated islets, GHS-R blockade and ghrelin immunoneutralization markedly enhanced glucose-induced increases in insulin release and cytosolic Ca^<2+> concentration ([Ca^<2+>]_i), while ghrelin at a relatively high concentration (10nM) suppressed insulin release. Ghr … More elin attenuated glucose-induced [Ca^<2+>]_i increases and increased delayed outward K^+ currents in single β-cells. These findings demonstrate that endogenous ghrelin in islets restricts glucose-induced insulin release via attenuating Ca^<2+> signaling and that this insulinostatic action is implicated in the upward control of blood glucose.We studied the effects of ghrelin and an anorectic hormone, leptin, on neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC), the neurons playing a central role in feeding. Ghrelin increased [Ca^<2+>]_i in ARC NPY neurons via phospholipase C-, adenylate cyclase- and protein kinase A (PKA)-mediated pathways. Ghrelin-induced [Ca^<2+>]_i increases were suppressed by subsequent administration of leptin. This reciprocal regulation by ghrelin and leptin may play an important role in the control of the ARC NPY neuron activity and, thereby, feeding.This study has revealed a novel function of ghrelin in regulation of insulin release and glucose metabolism and a neural signaling for orexigenic action of ghrelin. Together with the GH-releasing function, ghrelin may underlie the integrative regulation of energy homeostasis. Less

在该螺柱中，在胰岛胰岛中，胰岛素（GH）是胰岛素的，通过腹膜内注射特异性GHS-R拮抗剂，在胰岛胰岛素中表达了胰岛素。 （GTT）G葡萄糖在GTT期间，葡萄糖升高和胰岛素反应。胰岛素释放和胞质Ca^<2+>浓度（[Ca^<2+i），而在相对高浓度（10nm）下，胰岛素抑制了胰岛素释放，并增加了单个β-细胞中的延迟k^+电流。 。弧核（ARC）ASED [Ca^<2+>] _ I在磷脂酶C-，腺苷酸环酶和蛋白激酶A（PKA）介导的途径中的弧菌神经元中。在控制弧Npy神经元活性和喂养方面的重要作用。这项研究揭示了生长素蛋白在租赁和葡萄糖SM的法规中的新颖作用，以及用于GHRELIN的甲状腺素作用的神经信号。能量稳态的综合调节是基础。

项目成果

Idenitification of N-arachidonylglacine, U18666A, and 4-androstene-3, 17-dione as novel insulin Secretagogues.

鉴定 N-花生四烯基甘氨酸、U18666A 和 4-雄烯-3, 17-二酮作为新型胰岛素促分泌剂。

• 发表时间: 2005
• 期刊: Biochem Biophys Res Commun 333
• 作者: Hashimoto;M.;Maekawa F;Kuramochi M;Nakata M;Kuramochi M;Kuramochi M;Fujiwara K;Oneka T;Muroya S;Fujiwara K;Nakata M;Ikeda Y
• 通讯作者: Ikeda Y

Galanin-like peptide stimulates vasopressin, oxytocin and ACTH release in rats.

甘丙肽样肽刺激大鼠体内加压素、催产素和促肾上腺皮质激素的释放。

• 发表时间: 2005
• 期刊: Neuroreport 16
• 作者: Hashimoto;M.;Maekawa F;Kuramochi M;Nakata M;Kuramochi M;Kuramochi M;Fujiwara K;Oneka T
• 通讯作者: Oneka T

Orexins (Hypocretins) directly interacts with neuropeptide Y, POMC and glucose-responsive neurons to regulate Ca^<2+> signaling in a reciprocal manner to leptin : orexigenic neuronal pathways in the mediobasal hypothalamus.

食欲素(Hypocretins)直接与神经肽Y、POMC和葡萄糖反应性神经元相互作用，以与瘦素互惠的方式调节Ca^2信号传导：中基底下丘脑中的食欲产生神经元通路。

• 发表时间: 2004
• 期刊: Eur.J Neurosci. 19
• 作者: Hashimoto;M.;Maekawa F;Kuramochi M;Nakata M;Kuramochi M;Kuramochi M;Fujiwara K;Oneka T;Muroya S;Fujiwara K;Nakata M;Ikeda Y;Kuramochi M;Onaka T;Fujiwara K;Nakata M;Ikeda Y;Yada T;Fujiwara K;Ikeda Y;Muroya S;Yamada H;Nakata M;Dezaki K;Muroya S
• 通讯作者: Muroya S

Galanin-like peptide increases cytosolic Ca^2+ in neurons containing growth hormone-releasing hormone in the arcuate nucleus.

甘丙肽样肽可增加弓状核中含有生长激素释放激素的神经元中的胞质 Ca^2。

• 发表时间: 2005
• 期刊: Regulatory Peptides 126
• 作者: Hashimoto;M.;Maekawa F;Kuramochi M;Nakata M;Kuramochi M;Kuramochi M
• 通讯作者: Kuramochi M

グレリンと糖脂質代謝

生长素释放肽和糖脂代谢

• 发表时间: 2004
• 作者: Dezaki K;Yada T;Muroya S;Nakata M;Dezaki K;矢田俊彦;出崎克也
• 通讯作者: 出崎克也