위장내분비 L 세포와 췌장 베타세포의 기능에서 새로운 합성 GPR119의 효현제인 CKD 화합물의 효과
Effects of novel synthetic GPR119 agonists on enteroendocrine L-cell and pancreatic beta-cell function
- 주제(키워드) GPR119 , GLP-1
- 발행기관 아주대학교
- 지도교수 김욱
- 발행년도 2016
- 학위수여년월 2016. 2
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000021649
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
As GPR119, a G protein-coupled receptor 119 (GPR119) expressed primarily in pancreatic β cells and enteroendocrine L cells mediates insulin secretion from pancreatic β cells and glucagon-like peptide 1 (GLP-1) release from intestinal L cells, it has attracted significant interest as a promising drug target for the treatment of type 2 diabetes mellitus. Here I show the effects of three novel synthetic GPR119 agonists (CKD-1, CKD-2, and CKD-3) on GLP-1 secretion from GLUTag (intestinal L cell-line) cells as well as effects of CKD-2 on cell viability of MIN6 (pancreatic β cell-line) cells. All compounds dose-dependently increased GLP-1 release from GLUTag cells both under the low and high glucose conditions and these effects were mediated by GPR119. However, there was no effect on intracellular cAMP accumulation. GPR119 silencing by siRNA reduced proglucagon mRNA levels and, conversely, treatment of the compound increased proglucagon mRNA levels in GLUTag cells. In addition, CKD-2 dose-dependently enhanced MIN6-cell viability both under the low and high glucose conditions. Based on experimental data, these results suggest that novel synthetic GPR119 agonist CKD-1, CKD-2, and CKD-3 may be a potentially promising modulator to promote function of intestinal enteroendocrine L cells and pancreatic β cells.
more목차
Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS and METHODS 4
1. Cell culture 4
2. Immunofluorescence staining and image analysis 4
3. In vitro assays 5
4. Small interfering RNA transfection 5
5. RNA isolation and quantitative real-time PCR (qRT-PCR) 6
6. MTS assay 7
7. Statistical analysis 7
Ⅲ. RESULTS 8
1. GPR119 is present in enteroendocrine L and K cells and pancreatic β cells 8
2. CKD compounds stimulate GLP-1 secretion in the GPR119-dependent manner 13
3. CKD compounds increase levels of proglucagon mRNA 23
4. CKD-2 increases pancreatic β-cell viability 26
Ⅳ. DISCUSSION 29
Ⅴ. REFERENCE 32
Ⅵ. ABSTRACT IN KOREAN(국문초록) 39
