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

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Laura B James-AllanThomas Jansson

Abstract

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 mechani...Continue Reading

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Citations

Jul 1, 2020·Frontiers in Endocrinology·Stephanie ChidesterPaule V Joseph
Oct 22, 2020·Cellular and Molecular Life Sciences : CMLS·Caitlyn E BowmanMichael J Wolfgang
Dec 1, 2020·American Journal of Reproductive Immunology : AJRI·Rodolfo R FavaroUdo R Markert
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May 29, 2021·Frontiers in Immunology·Kunfeng BaiPhilip C N Chiu
Jul 10, 2021·Mediators of Inflammation·Zengfang WangXue Liu
Aug 22, 2021·Journal of Translational Medicine·Soumyalekshmi NairCarlos Salomon

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