Multiparity increases the risk of diabetes by impairing the proliferative capacity of pancreatic ß cells.
Exp Mol Med
; 55(10): 2269-2280, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37903900
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 ß cell proliferation were impaired in multiparous mice. The ß cells of multiparous mice exhibited aging features, including telomere shortening and increased expression of Cdkn2a. Single-cell RNA-seq analysis revealed that the ß 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 ß 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 ß cells, which impair their proliferative capacity to compensate for insulin resistance.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Diabetes Gestacional
/
Células Secretoras de Insulina
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article