AJOU Central Library Repository: 위장내분비 L 세포와 췌장 베타세포의 기능에서 새로운 합성 GPR119의 효현제인 CKD 화합물의 효과

위장내분비 L 세포와 췌장 베타세포의 기능에서 새로운 합성 GPR119의 효현제인 CKD 화합물의 효과

Alternative Title: Effects of novel synthetic GPR119 agonists on enteroendocrine L-cell and pancreatic beta-cell function

Alternative Abstract: 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.

Appears in Collections:: Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)

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