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  • 學位論文

果蠅腦中的胰島素生成細胞透過間隙連接調控胰島素分泌

Gap Junctions Mediate Insulin Secretion in Insulin-Producing Cells of the Drosophila Brain

指導教授 : 傅在峰
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摘要


神經與內分泌系統相互協調控制動物的許多生理現象,研究證實當黑腹果蠅(Drosophila melanogaster)的胰島素分泌細胞(insulin-producing cells; IPCs)功能失調所引發類胰島素胜肽(insulin-like peptide; Ilps)的大量分泌,將透過胰島素/類胰島素生長因子訊息傳遞途徑(insulin/insulin-like growth factor signaling; IIS)促使側咽腺(corpora allata; CA)大量生合成青春激素(juvenile hormone; JH),並使具有生物活性的蛻皮激素(20-hydroxyecdysone; 20E)的水平降低,然而上述內分泌訊息網絡的失衡參與IPCs活性的回饋調節的報導目前仍未多見。本研究初步證實蛻皮激素訊號於IPCs當中可能透過調節microRNA let-7調節胰島素的分泌釋放,並透過DIANA-microT-CDS線上標靶基因預測軟體與雙冷光素酶活性分析於初步證實細胞間隙連接(gap junction)的成員Innexin 2 (Inx2)表現受let-7抑制表現;最終證實IPCs的Inx2失調將導致胰島素分泌失衡、壽命縮短並改變飢餓、氧化壓力的耐受性,暗示蛻皮激素訊號可能經由let-7抑制Inx2並參與調節IPCs的Ilps分泌。

並列摘要


The nervous and endocrine systems coordinate and control many physiological processes in animals. Previous study have showed the abnormal secretion of insulin-like peptide (Ilps) of insulin-producing cells (IPCs) triggers the biosynthesis of juvenile hormone (JH) of corpora allata (CA) through the insulin/insulin-like growth factor signaling (IIS) pathway, which may in turn reduce the 20-hydroxyecdysone level in Drosophila melanogaster. This study further demonstrates that ecdysone signaling may involve in the negative feedback of IPCs activity and modulate the insulin secretion ability. Preliminary evidence suggests that ecdysone signaling may regulates IPCs activity by microRNA let-7. In addition, let-7 may modulate the expression of Innexin 2 (Inx2), a gap junction-forming protein. This was predicted using the target gene prediction software DIANA-microT-CDS, and was further confirmed by conducting a dual-luciferase reporter assay. Moreover, the deficiency of Inx2 in IPCs induces abnormal insulin secretion, decreased lifespan, starvation and oxidative stress tolerance, suggesting ecdysone signaling may regulate let-7 expression, which in turn inhibits the expression level of Inx2, ultimately modulating IPC activity.

並列關鍵字

Drosophila IPCs gap junction microRNA ecdysone insulin

參考文獻


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