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Regulation of glucose homeostasis by small extracellular vesicles in normal pregnancy and in gestational diabetes
Author(s) -
JamesAllan Laura B.,
Rosario Frederick J.,
Barner Kelsey,
Lai Andrew,
Guanzon Dominic,
McIntyre H. David,
Lappas Martha,
Powell Theresa L.,
Salomon Carlos,
Jansson Thomas
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902522rr
Subject(s) - gestational diabetes , glucose homeostasis , homeostasis , extracellular vesicles , pregnancy , endocrinology , diabetes mellitus , medicine , vesicle , extracellular , extracellular fluid , gestation , chemistry , biology , biochemistry , microbiology and biotechnology , insulin resistance , membrane , genetics
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.