CB1R에 의한 췌장 베타 새포의 사멸과 증식 조절
Regulation of Apoptosis and Proliferation by Cannabinoids in Pancreatic Beta Cells: Involvement of Bcl-2 and Cyclin D2
- 주제(키워드) pancreatic beta-cell , cannabinoid receptor , diabetes
- 발행기관 아주대학교
- 지도교수 김욱
- 발행년도 2015
- 학위수여년월 2015. 8
- 학위명 석사
- 학과 및 전공 일반대학원 분자과학기술학과
- 실제URI http://www.dcollection.net/handler/ajou/000000020334
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Recent reports have shown that cannabinoid 1 receptors (CB1Rs) are expressed in pancreatic β cells, where they induce cell death by directly inhibiting activation of insulin receptor. Here I report that anti-apoptotic protein Bcl-2 and cell cycle regulator Cyclin D2 are involved in cannabinoid-induced β-cell death and growth arrest. Treatment of MIN6 and βTC6 cells with a synthetic CB1R agonist WIN55,212-2 leads to decrease in the expression of Bcl-2 and Cyclin D2, in turn inducing an arrest of the cell cycle in the G0/G1 phase and caspase-3-dependent apoptosis. Consistently, genetic deletion and pharmacological blockade of CB1Rs leads to increased β-cell survival and proliferation after injury due to increased levels of Bcl-2 and Cyclin D2. These findings provide evidence for involvement of Bcl-2 and Cyclin D2 in the regulation of β-cell survival and growth and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and growth in diabetes.
more목차
Ⅰ. INTRODUCTION
Ⅱ. MATERIALS and METHODS
Ⅲ. RESULTS
1. Activation of CB1R with WIN55,212-2 induces β cell death and cell cycle arrest at G1 phase.
2. WIN55,212-2 leads to decreased levels of Bcl-2 and Cyclin D2 in pancreatic β cells.
3. CB1R blockade increases levels of Cyclin D2 and Bcl-2 in pancreatic β cells of STZ-treated and db/db mice.
Ⅳ. DISCUSSION
Ⅴ. REFERENCE
Ⅵ. ABSTRACT IN KOREAN(국문초록)
