Regulation of glucose homeostasis by small extracellular vesicles in normal pregnancy and in gestational diabetes.

Autor: James-Allan LB; Division of Reproductive Sciences, Department of Obstetrics/Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Rosario FJ; Division of Reproductive Sciences, Department of Obstetrics/Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Barner K; Division of Reproductive Sciences, Department of Obstetrics/Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Lai A; Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine and Biomedical Sciences, The University of Queensland, Herston, QLD, Australia., Guanzon D; Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine and Biomedical Sciences, The University of Queensland, Herston, QLD, Australia., McIntyre HD; Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine and Biomedical Sciences, The University of Queensland, Herston, QLD, Australia.; Mater Health Services and Mater Medical Research Institute, Faculty of Medicine, University of Queensland, South Brisbane, QLD, Australia., Lappas M; Department of Obstetrics and Gynecology, University of Melbourne, Melbourne, VIC, Australia., Powell TL; Section for Neonatology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Salomon C; Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine and Biomedical Sciences, The University of Queensland, Herston, QLD, Australia.; Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile., Jansson T; Division of Reproductive Sciences, Department of Obstetrics/Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2020 Apr; Vol. 34 (4), pp. 5724-5739. Date of Electronic Publication: 2020 Mar 10.
DOI: 10.1096/fj.201902522RR
Abstrakt: The mechanisms underpinning maternal metabolic adaptations to a healthy pregnancy and in gestational diabetes mellitus (GDM) remain poorly understood. We hypothesized that small extracellular vesicles (sEVs) isolated from healthy pregnant women promote islet glucose-stimulated insulin secretion (GSIS) and peripheral insulin resistance in nonpregnant mice and that sEVs from GDM women fail to stimulate insulin secretion and cause exacerbated insulin resistance. Small EVs were isolated from plasma of nonpregnant, healthy pregnant, and GDM women at 24-28 weeks of gestation. We developed a novel approach in nonpregnant mice involving a mini-osmotic pump for continuous 4-day jugular venous infusion of sEVs and determined their effects on glucose tolerance in vivo and islets and skeletal muscle in vitro. Fasting insulin was elevated in mice infused with pregnant sEVs as compared to sEVs from nonpregnant and GDM women. Mice infused with sEVs from GDM women developed glucose intolerance. GSIS was increased in mice infused with healthy pregnancy sEVs compared to mice receiving nonpregnant sEVs. GSIS and muscle basal insulin signaling, and insulin responsiveness were attenuated in mice infused with GDM sEVs. sEVs represent a novel mechanism regulating maternal glucose homeostasis in pregnancy and we speculate that altered sEV content contributes to the development of GDM.
(© 2020 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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