The Mechanism of Inhibition of Insulin Secretion by Ghrelin

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590991
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Wakayama Medical University
• Principal Investigator: NISHI Masahiro 和歌山県立医科大学, 医学部, 准教授 (90228148)
• Project Period (FY): 2010 – 2012
• Keywords: 糖尿病 / インスリン分泌 / グレリン / IA-2β / AMPK / UCP2 / 酸化ストレス / シグナル伝達

Research Abstract

Ghrelin has been reported to show various effects including the secretion of growth hormone or the stimulation of appetite etc. Ghrelin has also been reported to inhibit insulin secretion. We have reported that ghrelin could inhibit insulin secretion via induction of IA-2beta (Doi A. et al. PNAS 103:885,2006). In this study, other than IA-2beta, involvement of AMPK/UCP2 pathway in this ghrelin’s effects on the inhibition of insulin secretion was identified (Wang Y et al. FEBS Lett 584:1503,2010). Since UCP2 has protective effects against oxidative stress, the protective effects of ghrelin on cell proliferation and apoptosis against oxidative stress were investigated, and ghrelin, dose-dependently, ameliorated decreased cell proliferation and increased apoptosis induced by H2O2 in MIN6 cells. However, unexpectedly, this ghrelin’s effects was not via AMPK-UCP2 pathway, but MAPK and PI3K pathways. Therefore, ghrelin has complicated effects on beta cells and glucose metabolism. Ghrelin does inhibit insulin secretion, bad for glucose metabolism, however, ghrelin also showed protective effects against oxidative stress, good for glucose metabolism. Further clarification of these ghrelin’s effects on beta cells will be necessar y.

Research Products

• [Journal Article] Ghrelin Inhibits Insulin Secretion through AMPK-UCP2 Pathway in β (2010)
  • Author(s): Ying Wang, Masahiro Nishi, Asako Doi, Takeshi Shono, Yasushi Furukawa, Takeshi Shimada, Hiroto Furuta, Hideyuki Sasaki, Kishio Nanjo
  • Journal Title: Cells FEBS Letters Volume: 584 Pages: 1503-1508
  • Peer Reviewed
• [Presentation] Ghrelin Protect Beta Cells From Oxidative Stress Via Both MAPK And PI3K Pathways. (2013)
  • Author(s): Masahiro Nishi, Wang Ying, Tatsuya Ishibashi, Asako Doi, Hiroto Furuta,Hideyuki Sasaki, Kishio Nanjo, Takashi Akamizu
  • Organizer: American Diabetes Association's 73rd Scientific Sessions
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 20130621-25
• [Presentation] グレリンは酸化ストレスによるβ細胞障害を防止する (2013)
  • Author(s): 西 理宏、王 穎、石橋達也、土井麻子、古田浩人、佐々木秀行、南條輝志男、赤水尚史
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本
  • Year and Date: 20130516-18
• [Presentation] The Effects of Ghrelin on Beta Cells -Inhibitor of Insulin Secretion or Lifesaver from Oxidative Stress-βCell Workshop 2013 (2013)
  • Author(s): Masahiro Nishi, Ying Wang, TatsuyaIshibashi, Asako Doi, Hiroto Furuta, Hideyuki Sasaki, Kishio Nanjo, TakashiAkamizu
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20130423-26
• [Presentation] Ghrelin Restores Decreased Cell Viability of Beta Cell Line by Oxidative Stress (2012)
  • Author(s): Masahiro Nishi, Ying Wang, Tatsuya Ishibashi, Asako Doi, Hiroto Furuta, Hideyuki Sasaki, Kishio Nanjo, Takashi Akamizu
  • Organizer: 9th International Diabetes FederationWestern Pacific Region Congress/4th Asian Association for Study of Diabetes
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20121124-27
• [Presentation] Ghrelin Inhibits Insulin Secretion via AMPK-UCP2 Pathway (2011)
  • Author(s): asahiro Nishi, Ying Wang, Asako Doi, Hiroto Furuta, Hideyuki Sasaki, KishioNanjo, Takashi Akamizu
  • Organizer: International Symposium "Computational Physiology of Cardiac Myocytes and Pancreatic β-cells; Interaction between Energy Metabolism and Membrane Excitability
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2011-01-30
• [Presentation] Ghrelin Activates AMPK-UCP2 Pathway and Inhibits Insulin Secretion in βCells (2010)
  • Author(s): Ying Wang, Masahiro Nishi, Asako Doi, Takeshi Shono, Yasushi Furukawa, Takeshi Shimada, Hiroto Furuta, Hideyuki Sasaki, Kishio Nanjo
  • Organizer: American Diabetes Association's 70th Scientific Sessions
  • Place of Presentation: Orland, USA
  • Year and Date: 20100625-29