Mining of novel granin-derived bioactive peptides that regulate insulin secretion.

• Project/Area Number: 23591358
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: University of Miyazaki
• Principal Investigator: YAMAGUCHI Hideki 宮崎大学, 医学部, 講師 (10305097)
• Co-Investigator(Kenkyū-buntansha): TOSHINAI Koji 宮崎大学, 医学部, 講師 (80381101) ; 松尾 崇 宮崎大学, 医学部, その他 (10404427)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 生理活性ペプチド / 糖尿病 / インスリン / 膵β細胞

Research Abstract

To explore the physiological roles of NERP-2 in the pancreas, we examined its effects on insulin secretion. We detected NERP-2 immunoreactivity in pancreatic islets, where it co-localized extensively with insulin. NERP-2 increased glucose-stimulated insulin secretion (GSIS) in a dose-dependent manner from isolated mouse pancreatic islets. NERP-2 significantly augmented GSIS after administration to rodents. Neither NERP-1 nor NERP-2-Gly (non-amidated NERP-2) stimulated insulin secretion. Calcium-imaging analysis demonstrated that NERP-2 increased the calcium influx in MIN6 cells. These findings show that NERP-2 is a novel bioactive peptide to stimulate insulin secretion.

Research Products

• [Journal Article] Neuroendocrine regulatory peptide-1 and -2 (NERPs) inhibit the excitability of magnocellular neurosecretory cells in the hypothalamus (2014)
  • Author(s): Toshinai K, Saito T, Yamaguchi H, Sasaki K, Tsuchimochi W,Minamino N, Ueta Y, Nakazato M
  • Journal Title: Brain Res Volume: (in press)
  • Peer Reviewed
• [Journal Article] Neuroendocrine regulatory peptide-1 and -2 (NERPs) inhibit the excitability of magnocellular neurosecretory cells in the hypothalamus. (2014)
  • Author(s): Toshinai K, Saito T, Yamaguchi H, Sasaki K, Tsuchimochi W, Minamino N, Ueta Y, Nakazato M
  • Journal Title: Brain Res Volume: 1563 Pages: 52-60
  • DOI: 10.1016/j.brainres.2014.03.038
  • Peer Reviewed / Open Access
• [Journal Article] Ghrelin prevents the development of experimental diabetic neuropathy in rodents (2013)
  • Author(s): Tsuchimochi W, Kyoraku I, Yamaguchi H, Toshinai K, Shiomi K, Kangawa K, Nakazato M
  • Journal Title: Eur J Pharmacol Volume: 702 Pages: 187-193
  • Peer Reviewed
• [Journal Article] Neuroendocrine regulatory peptide-2 stimulates glucose-induced insulin secretion in vivo and in vitro (2012)
  • Author(s): Yamaguchi H, Moin AH, Rhee M ,Kim JW, Toshinai K, Waise TMZ, Naznin F, Matsuo T, Sasaki K, Minamino N, Yoon KH, Nakazato M
  • Journal Title: Biochem Biophys Res Commun Volume: 428 Pages: 512-517
  • Peer Reviewed
• [Journal Article] Intestinal fatty acid infusion modulates food preference as well as calorie intake via the vagal nerve and midbrain-hypothalamic neural pathways in rats (2012)
  • Author(s): Ogawa N, Ito M, Yamaguchi H, Shiuchi T, Okamoto S, Wakitani K, Minokoshi Y, Nakazato M
  • Journal Title: Metabolism Volume: 61 Pages: 1312-1320
  • Peer Reviewed
• [Journal Article] Intestinal fatty acid infusion modulates food preference as well as calorie intake via the vagal nerve and midbrain-hypothalamic neural pathways in rats (2012)
  • Author(s): Ogawa N, et al
  • Journal Title: Metabolism Volume: 61 Issue: 9 Pages: 1312-1320
  • DOI: 10.1016/j.metabol.2012.02.011
  • Peer Reviewed
• [Journal Article] Neuroendocrine regulatory peptide-2 stimulates glucose-induced insulin secretion in vivo and in vitro. (2012)
  • Author(s): Moin AS, Yamaguchi H, Rhee M, Kim JW, Toshinai K, Waise TM, Naznin F, Matsuo T, Sasaki K, Minamino N, Yoon KH, Nakazato M
  • Journal Title: Biochem Biophys Res Commun Volume: 428 Issue: 4 Pages: 512-517
  • DOI: 10.1016/j.bbrc.2012.10.073
  • Peer Reviewed
• [Journal Article] Therapeutic potential of ghrelin treatment for unloading-induced muscle atrophy in mice (2011)
  • Author(s): Koshinaka K, Toshinai K, Mohammad A, Noma K, Oshikawa M, Ueno H, Yamaguchi H, Nakazato M
  • Journal Title: Biochem Biophys Res Commun Volume: 412 Pages: 296-301
  • Peer Reviewed
• [Presentation] NERP-1とNERP-2のバソプレシン分泌調節機能の解析 (2013)
  • Author(s): 十枝内厚次、斉藤健、山口秀樹、佐々木一樹、南野直人、上田陽一、中里雅光
  • Organizer: 第17回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Functional analyses of Neuroendocrine regulatory peptide-2 (NERP-2) in regulating glucose stimulated insulin secretion in vitro and in vivo (2013)
  • Author(s): モイン・アブサレーエムディ、十枝内厚次、山口秀樹、佐々木一樹、南野直人、中里雅光
  • Organizer: 第17回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 大阪
• [Presentation] NERP-2のオレキシン系を介したエネルギー代謝調節 (2013)
  • Author(s): 十枝内厚次、山口秀樹、佐々木一樹、影山晴秋、塩田清二、南野直人、中里雅光
  • Organizer: 第40回日本神経内分泌学会
  • Place of Presentation: 宮崎
• [Presentation] 新規生理活性ペプチドNERPの膵β細胞での機能解析 (2013)
  • Author(s): 山口秀樹、モイン・アブサレーエムディ、松尾崇、十枝内厚次、佐々木一樹、南野直人、中里雅光
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
• [Presentation] Neuroendocrine regulatory peptide-2 (NERP-2) is a novel regulator of glucose stimulated insulin secretion in rodents (2013)
  • Author(s): モイン・アブサレーエムディ、山口秀樹、十枝内厚次、佐々木一樹、南野直人、中里雅光
  • Organizer: 第86回日本内分泌学会学術集会
  • Place of Presentation: 仙台
• [Presentation] Functional analyses of Neuroendocrine regulatory peptide-2 (NERP-2) in regul ating glucose stimulated insulin secretion in vitro and in vivo (2013)
  • Author(s): モイン・アブサレーエムディ、十枝内 厚次、山口 秀樹、佐々木 一樹、南野 直人、中里 雅光
  • Organizer: 第17回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 大阪
• [Presentation] 新規生理活性ペプチドNERP-2の局在と機能 (2012)
  • Author(s): 松尾崇、山口秀樹、モイン・アブサレー、十枝内厚次、影山晴秋、佐々木一樹、南野直人、塩田清二、中里雅光
  • Organizer: 第39回日本神経内分泌学会学術集会
  • Place of Presentation: 北九州
• [Presentation] Neuroendocrine regulatory peptides (NERPs) in regulating feeding and hormone secretions (2012)
  • Author(s): Yamaguchi H, Toshinai K, Matsuo T, Kageyama H, Sasaki K, Shioda S, Minamino N, Nakazato M
  • Organizer: 第3回国際神経ペプチド学会日本支部主催国際シンポジウムThe 3rd Japan INPS Meeting
  • Place of Presentation: 北九州
• [Presentation] Neuroendocrine regulatory peptide-2 (NERP-2) is a novel regulator of glucose-stimulated insulin secretion in rodents (2012)
  • Author(s): Abu Saleh Md. Moin、山口秀樹、松尾崇、十枝内厚次、佐々木一樹、南野直人、中里雅光
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 新規生理活性ペプチドNERP-2のマウス膵での局在 (2012)
  • Author(s): 松尾崇、山口秀樹、十枝内厚次、影山晴秋、佐々木一樹、南野直人、塩田清二、中里雅光
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] NERPsによるバソプレシン分泌調節機序の解析 (2012)
  • Author(s): 十枝内厚次、齋藤健、山口秀樹、佐々木一樹、南野直人、上田陽一、中里雅光
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Neuroendocrine regulatory peptides (NERPs) in regulating feeding and hormone secretions (2012)
  • Author(s): Yamaguchi H, Toshinai K, Matsuo T, Kageyama H, Sasaki K, Shioda S, Minamino N, Nakazato M
  • Organizer: 第3回国際神経ペプチド学会日本支部主催 国際シンポジウム
  • Place of Presentation: 北九州
• [Presentation] 新規生理活性ペプチドNeuroendocrine regulatory peptides (NERPs)のヒト組織での局在 (2011)
  • Author(s): 松尾崇、山口秀樹、影山晴秋、佐々木一樹、塩田清二、南野直人、中里雅光
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 神戸
• [Presentation] NERP-2の摂食およびエネルギー代謝調節作用 (2011)
  • Author(s): 十枝内厚次、山口秀樹、影山晴秋、松尾崇、佐々木一樹、塩田清二、南野直人、中里雅光
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 神戸
• [Presentation] Neuroendocrine regulatory peptides (NERPs) localize in human neurons and endocrine tissues (2011)
  • Author(s): Yamaguchi H, Matsuo T, Kageyama H, Sasaki K, Shioda S, Minamino N, Nakazato M
  • Organizer: 93rd Annual Meeting of the Endocrine Society
  • Place of Presentation: Boston, USA
• [Presentation] Neuroendocrine regulatory peptide-2 regulates feeding behavior via the orexin system in the hypothalamus (2011)
  • Author(s): Matsuo T, Toshinai K, Kageyama H, Yamaguchi H, Sasaki K, Shioda S, Minamino N, Nakazato M
  • Organizer: 93rd Annual Meeting of the Endocrine Society
  • Place of Presentation: Boston, USA
• [Book] 下垂体炎、尿崩症産科と婦人科80巻増刊号ホルモン療法実践マニュアル (2013)
  • Author(s): 山口秀樹、鮫島浩、中里雅光
  • Publisher: 診断と治療社
• [Book] グレリンとオベスタチン、内分泌・糖尿病・代謝内科、36巻 (2013)
  • Author(s): 山口秀樹、上野浩晶、中里雅光
  • Publisher: 科学評論社
• [Book] 産科と婦人科 80巻増刊号 ホルモン療法実践マニュアル (2013)
  • Author(s): 山口秀樹、鮫島浩、中里雅光
  • Total Pages: 372
  • Publisher: 診断と治療社
• [Book] 内分泌・糖尿病・代謝内科 特別増刊号 (2013)
  • Author(s): 山口秀樹、上野浩晶、中里雅光
  • Total Pages: 513
  • Publisher: 科学評論社
• [Book] 実験医学増刊代謝・内分泌ネットワークと医薬応用生理活性ペプチドと疾患・臨床応用 (2011)
  • Author(s): 山口秀樹、中里雅光(児島将康,斎藤祐見子,中里雅光編)
  • Publisher: 羊土社(東京)
• [Book] 実験医学増刊 代謝・内分泌 ネットワークと医薬応用 (2011)
  • Author(s): 山口秀樹、中里雅光 ：児島将康, 斎藤祐見子, 中里雅光編,
  • Total Pages: 212
  • Publisher: 羊土社（東京）