초록

● 베타세포의 분화 및 증식 조절 기전 규명
● 작업부하 및 glucokinase와 베타세포 증식기전의 관계 규명
● 베타세포의 증식조절에 관여하는 G-protein coupled receptor(GPCR)의 규명
● 생체환경 모사 시스템을 이용한 베타세포의 3차원 배양 및 베타세포 증식 조절
● 에너지 대사에서 세로토닌의 역할 규명
● 베타세포 특이적 형질전환 마우스를 이용한 세로토닌 발현 분석
● 췌도 발달과 기능 유지에서 PRMT1의 역할 규명

Abstract ▼

1. Purpose and contents
Diabetes mellitus became an enoumous socioeconomic burden and is a leading cause of death. It is not curable until now. Decrease of insulin secretion is the common pathophysiology of type 1 diabetes, type 2 diabetes, and gestational diabetes. Although Asians, including Kor

1. Purpose and contents
Diabetes mellitus became an enoumous socioeconomic burden and is a leading cause of death. It is not curable until now. Decrease of insulin secretion is the common pathophysiology of type 1 diabetes, type 2 diabetes, and gestational diabetes. Although Asians, including Koreans, have lower insulin resistance than Caucasians, they have less amount of pancreatic β cell mass and are relatively susceptible to diabetes. During pregnancy insulin resistance increases, so that compensation by β cell occurs. Serotonin plays a key role in this process. In this research, I propose to identify the molecular mechanism how Tph1 gene expression is regulated in β cell specific manner, to identify the role of serotonin in the regulation of β cell proliferation during perinatal period, to confirm the serotonin receptor that is responsible for the regulation of beta cell proliferation by serotonin, and to test the possibility of perinatal tryptophan deficiency as a cause of diabetes in adult. My proposed studies will help to understand how β cell proliferation is regulated, to develop new strategies to expand β cells in vitro and in vivo for the people with diabetes and to develop new drug to cure or prevent diabetes.

2. Result
● Identification of molecular mechanism of beta cell differentiation and proliferation
● Identification of molecular mechanism of beta cell workload and control of workload using serotonin
● Identification of G-protein coupled receptor(GPCR) which involve in beta cell proliferation
● Regulation of beta cell proliferation by using 3D culture platform
● Identification of role of serotonin in energy metabolism
● Investigation of serotonin expression by using beta cell specific transgenic&K/O mice
● Identification of role of PRMT1 in islet development and physiology

3. Expected contribution
● To support theoretical basis of new kind of antidiabetic drug
● To find genes that cause diabetes related with serotonin in Korea and to provide early diagnosis
● To develop methods which treat or delay diabetes by proliferating β cells