2005 Fiscal Year Final Research Report Summary
Regulation by endogenous ghrelin of insulin release, feeding and glucose metabolism
| Project/Area Number |
16390053
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | JICHI MEDICAL UNIVERSITY |
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Principal Investigator |
YADA Toshihiko JICHI MEDICAL UNIVERSITY, School of Medicine, Department of Physiology, Professor, 医学部, 教授 (60166527)
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| Co-Investigator(Kenkyū-buntansha) |
ONAKA Tatsushi JICHI MEDICAL UNIVERSITY, School of Medicine, Department of Physiology, associate professor, 医学部, 助教授 (90177254)
NAKATA Masanori JICHI MEDICAL UNIVERSITY, School of Medicine, Department of Physiology, Lecturer, 医学部, 講師 (10305120)
DEZAKI Katsuya JICHI MEDICAL UNIVERSITY, School of Medicine, Department of Physiology, Assistant, 医学部, 助手 (90337329)
SONE Hideyuki JICHI MEDICAL UNIVERSITY, School of Medicine, Department of Physiology, Research worker, 医学部, 研究員 (90398511)
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| Project Period (FY) |
2004 – 2005
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| Keywords | ghrelin / insulin release / β-cells / cytosolic Ca^<2+> / plasma glucose / feeding center / NPY neuron / leptin |
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| Research Abstract |
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
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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
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[Book] グレリンと糖脂質代謝2004
Author(s)
出崎克也
Total Pages
388-391
Publisher
日本臨床 第2巻 増刊号9
Description
「研究成果報告書概要(和文)」より
