Regulation of glucose homeostasis by small extracellular vesicles in normal pregnancy and in gestational diabetes
| Autor: | Theresa L. Powell, Andrew Lai, Martha Lappas, Thomas Jansson, Laura B. James-Allan, Carlos Salomon, Dominic Guanzon, Kelsey Barner, Frederick J Rosario, H. David McIntyre |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Blood Glucose medicine.medical_specialty endocrine system diseases viruses medicine.medical_treatment Biochemistry 03 medical and health sciences Extracellular Vesicles Mice 0302 clinical medicine Insulin resistance Pregnancy Diabetes mellitus Internal medicine Glucose Intolerance Insulin Secretion Genetics Medicine Glucose homeostasis Animals Homeostasis Humans Molecular Biology business.industry Insulin virus diseases respiratory system medicine.disease Gestational diabetes Mice Inbred C57BL Diabetes Gestational 030104 developmental biology Endocrinology Gestation Female Insulin Resistance business 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(4) |
| ISSN: | 1530-6860 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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