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分泌型細胞自噬反應在胰島素釋放與第二型糖尿病之角色

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國立成功大學「邁向頂尖大學計畫」

延攬優秀人才工作報告表

NCKU’s “Aim for the Top University Project”

Work Report Form for Distinguished Scholars

□續聘continuation of employment ■離職resignation

100 年 7 月 13 日更新 受聘者姓名

Name of the Employee

藍昇輝 ■男 女

Male Female

聘 期 Period of Employment

from 104 年(y) 8 月(m) 1 日(d) to 105 年(y) 8 月(m)31 日(d) 研究或教學或科技研發與

管理計畫名稱 The project title of research,

teaching, technology development and management

分泌型細胞自噬反應在胰島素 釋放與第二型糖尿病之角色

計畫主持人

(申請單位主管)

Project Investigator (Head of Department/Center)

劉校生 特聘教授 醫學院微免所

補助延聘編號

Grant Number HUA 105- 3 - 7 -052

一、 研究、教學、科技研發與管理工作全程經過概述。(由受聘人填寫)

Please summarize the entire research, teaching, or science and technology R&D and management work process (To be completed by the employee)

1. To clarify the role of autophagy in insulin secretion in β-cell

We used autophagy inducers and inhibitors to manipulate autophagy activity, and proved that autophagy positively regulates insulin secretion. Therefore, the lower autophagic activity of cell lines which are established from Min-6 cells by silencing Atg5 and Atg7 expression also confirmed that autophagy is essential mechanism for glucose stimulation insulin secretion.

2. To clarify the underlying mechanism of secretory autophagy regulation of insulin secretion

The autophagosomes were purified from Min-6 cells and identified engulfed protein by LC-MS/MS.

We demonstrated that autophagy engulfed whole insulin granules and identified Rab37 is a novel protein for autophagosome fusion with insulin granules. In addition, we created Rab37(-/-) cell line from Min-6 cells by CRISPR system and proved that Rab37 mediated secretory autophagy for autophagosome trafficking and autophagy related insulin secretion.

3. To clarify the role of autophagy in insulin secretion in vivo

We enhanced autophagy activity in B6 mice through fed autophagy inducer (Niclosamide) in diet.

In Niclosamide group, insulin level of blood was significantly upregulated and the the regulation ability of glucose homeostasis was improved. These data indicated that enhanced autophagy activity promotes insulin secretion in vivo.

4. To clarify the correlation between autophagy and insulin secretion in Type-II DM animal and clinical specimens

In two Type-II DM animal models including ob/ob mice and high fat diet induced mice, autophagy was activate and among colocalized with insulin granules inβ-cells. We further enhanced autophagy activity in B6 mice through fed autophagy inducer (Niclosamide) in high fat diet. Our data demonstrated that induction of autophagy improved hyperglycemia in type-II DM mice through enhancing insulin secretion.

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二、研究或教學或科技研發與管理成效評估(由計畫主持人或單位主管填寫

Please evaluate the performance of research, teaching or science and technology R&D and management Work: (To be completed by Project Investigator or Head of Department/Center)

(1)是否達到延攬預期目標?

Has the expected goal of recruitment been achieved?

是。接達成預定之相關目標。

(2)研究或教學或科技研發與管理的方法、專業知識及進度如何?

What are the methods, professional knowledge, and progress of the research, teaching, or R&D and management work?

在此計畫:分泌型細胞自噬反應在胰島素釋放與第二型糖尿病之角色。已經利用細胞實驗和小 鼠模式證實相關實驗成果。

(3)受延攬人之研究或教學或科技研發與管理成果對該計畫(或貴單位)助益如何?

How have the research, teaching, or R&D and management results of the employed person given benefit to the project (or your unit)?

藍昇輝博士在此計畫期間主要掌控個子項計畫進度與實驗之進行,並在期限內將預計計畫內 容完成。

(4)受延攬人於補助期間對貴單位或國內相關學術科技領域助益如何?

How has the employed person, during his or her term of employment, benefited your unit or the relevant domestic academic field?

藍昇輝博士於此計畫之研究成果即將投送發表於國際期刊,對於該領域而言,將會提供一個 創新且具潛力的概念,未來將有利於糖尿病之治療。

(5)具體工作績效或研究或教學或科技研發與管理成果:

Please describe the specific work performance, or the results of research, teaching, or R&D and management work:

藍昇輝博士於此架化期間參與兩個研討會並發表成果之海報競賽,皆得到獎項,代表此研究 之成果得到肯定。

2016 年第 24 屆細胞及分子生物新知研討會壁報獎 2015 年台灣生物化學及分子生物學會秋令營壁報獎

(6)是否續聘受聘人? Will you continue hiring the employed person? □續聘Yes ■不續聘No

※ 此報告表篇幅以三~四頁為原則。This report form should be limited to 3-4 pages in principle.

※ 此表格可上延攬優秀人才成果報告繳交說明網頁下載。

This report form can be downloaded in http://scholar.lib.ncku.edu.tw/explain/

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