Oral Presentation ESA-SRB 2023 in conjunction with ENSA

Repeated delivery increases the risk of diabetes by impairing the proliferation of pancreatic β cells (#80)

Joon Ho Moon 1 2 , Joonyub Lee 2 , Hail Kim 2
  1. Seoul National University, Seongnam, South Korea
  2. Korea Advanced Institute of Science and Technology, Daejeon, South Korea

Pregnancy imposes a substantial metabolic burden on women. We have reported than lactation improves pancreatic β cell mass and function in postpartum women1,2,3, but little is known about whether or how repeated delivery increase the risk of maternal postpartum diabetes. In this study, we assessed the metabolic impact of multiple pregnancies in humans and a rodent model. Mice underwent multiple pregnancies had increased adiposity and insulin resistance developed but insulin secretory function and compensatory pancreatic β cell proliferation were impaired in multiparous mice compared to age-matched virgin 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 are 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.

  1. Moon JH, Kim H, Kim H, Park J, Choi W, Choi W, Hong HJ, Ro H-J, Jun S, Choi SH, Banerjee RR, Shong M, Cho NH, Kim SK, German MS, Jang HC, Kim H. Lactation improves pancreatic β cell mass and function through serotonin production, Sci Transl Med, 2020 Apr 29; 12: eaay0455 (2020).
  2. Moon JH, Jang HC. Gestational Diabetes Mellitus: Diagnostic approaches and maternal-offspring complications. Diabetes Metab J, 2022; 46(1):3-14.
  3. Choi W, Moon JH, Kim H. Serotonergic regulation of energy metabolism in peripheral tissues, J Endocrinol, 2020 Apr;245(1):R1-R10.