한빛사논문
- 조회427
KAIST, 가톨릭대학교 서울성모병원
Joon Ho Moon 1,2,7, Joonyub Lee 1,3,7, Kyun Hoo Kim 1,4,7, Hyun Jung Kim 1, Hyeongseok Kim 1,5, Hye-Na Cha 6, Jungsun Park 1, Hyeonkyu Lee 1, So-young Park 6, Hak Chul Jang 2,* and Hail Kim 1,4,*
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
2Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea.
3Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
4Biomedical Research Center, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
5Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Korea.
6Department of Physiology, College of Medicine, Yeongnam University, Daegu, Korea.
7These authors contributed equally: Joon Ho Moon, Joonyub Lee, Kyun Hoo Kim.
*Corresponding authors: correspondence to Hak Chul Jang or Hail Kim
Abstract
Pregnancy imposes a substantial metabolic burden on women, but little is known about whether or how multiple pregnancies increase the risk of maternal postpartum diabetes. In this study, we assessed the metabolic impact of multiple pregnancies in humans and in a rodent model. Mice that underwent multiple pregnancies had increased adiposity, but their glucose tolerance was initially improved compared to those of age-matched virgin mice. Later, however, insulin resistance developed over time, but insulin secretory function and compensatory pancreatic β cell proliferation were impaired in multiparous mice. The β cells of multiparous mice exhibited aging features, including telomere shortening and increased expression of Cdkn2a. Single-cell RNA-seq analysis revealed that the β cells of multiparous mice exhibited upregulation of stress-related pathways and downregulation of cellular respiration- and oxidative phosphorylation-related pathways. In humans, women who delivered more than three times were more obese, and their plasma glucose concentrations were elevated compared to women who had delivered three or fewer times, as assessed at 2 months postpartum. The disposition index, which is a measure of the insulin secretory function of β cells, decreased when women with higher parity gained body weight after delivery. Taken together, our findings indicate that multiple pregnancies induce cellular stress and aging features in β cells, which impair their proliferative capacity to compensate for insulin resistance.
논문정보
- Research article
- 2023년 10월 (BRIC 등록일 2023-11-15)
- 국내 연구진
- 의약학 > 분자세포의학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 논문보기
