The Mechanism of Inhibition of Insulin Secretion by Ghrelin

Ghrelin抑制胰岛素分泌的机制

• 批准号: 22590991
• 负责人: NISHI Masahiro
• 金额: $ 2.25万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590991/
• 关键词: 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; AMPキナーゼ

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.

Ghrelin具有多种作用，包括分泌生长激素或刺激食欲等。Ghrelin还具有抑制胰岛素分泌的作用。我们已经报道ghrelin可以通过诱导IA-2 β抑制胰岛素分泌（Doi A.等人PNAS 103：885，2006）。在该研究中，除了IA-2 β，还鉴定了AMPK/UCP 2途径参与该生长素释放肽对胰岛素分泌抑制的作用（Wang Y等，FEBS Lett 584：1503，2010）。由于UCP 2具有抗氧化应激的保护作用，因此研究了ghrelin对细胞增殖和凋亡的抗氧化应激的保护作用，并且ghrelin剂量依赖性地改善了由H2 O2诱导的MIN 6细胞的细胞增殖降低和细胞凋亡增加。然而，出乎意料的是，这种ghrelin的作用不是通过AMPK-UCP 2途径，而是通过MAPK和PI 3 K途径。因此，ghrelin对β细胞和葡萄糖代谢具有复杂的作用。Ghrelin确实抑制胰岛素分泌，不利于葡萄糖代谢，然而，Ghrelin也显示出对氧化应激的保护作用，有利于葡萄糖代谢。这些ghrelin对β细胞的影响的进一步澄清将是必要的。

项目成果

Ghrelin Inhibits Insulin Secretion through AMPK-UCP2 Pathway in β

Ghrelin 通过 AMPK-UCP2 通路抑制 β 胰岛素分泌

• 发表时间: 2010
• 期刊: Cells FEBS Letters
• 作者: Ying Wang;Masahiro Nishi;Asako Doi;Takeshi Shono;Yasushi Furukawa;Takeshi Shimada;Hiroto Furuta;Hideyuki Sasaki;Kishio Nanjo
• 通讯作者: Kishio Nanjo

Ghrelin Restores Decreased Cell Viability of Beta Cell Line by Oxidative Stress

生长素释放肽可恢复因氧化应激而降低的 β 细胞系细胞活力

• 发表时间: 2012
• 作者: Masahiro Nishi;Ying Wang;Tatsuya Ishibashi;Asako Doi;Hiroto Furuta;Hideyuki Sasaki;Kishio Nanjo;Takashi Akamizu
• 通讯作者: Takashi Akamizu

Ghrelin Protect Beta Cells From Oxidative Stress Via Both MAPK And PI3K Pathways.

Ghrelin 通过 MAPK 和 PI3K 途径保护 β 细胞免受氧化应激。

• 发表时间: 2013
• 作者: Masahiro Nishi;Wang Ying;Tatsuya Ishibashi;Asako Doi;Hiroto Furuta,Hideyuki Sasaki;Kishio Nanjo;Takashi Akamizu
• 通讯作者: Takashi Akamizu

グレリンは酸化ストレスによるβ細胞障害を防止する

Ghrelin 可预防氧化应激引起的 β 细胞损伤

• 发表时间: 2013
• 作者: 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
• 通讯作者: 赤水尚史

Ghrelin inhibits insulin secretion through AMP-UCP2 pathway in β cells

Ghrelin通过AMP-UCP2通路抑制β细胞胰岛素分泌

• 发表时间: 2010
• 期刊: FEBS Letters
• 影响因子: 3.5
• 作者: Y Wang;M Nishi;et al.
• 通讯作者: et al.