Human gestational diabetes mellitus-derived exosomes impair glucose homeostasis in pregnant mice and stimulate functional maturation of offspring-islets

Quick Facts

  • Publication title: Human gestational diabetes mellitus-derived exosomes impair glucose homeostasis in pregnant mice and stimulate functional maturation of offspring-islets
  • Journal: Life Sci
  • Year: 2024
  • DOI: 10.1016/j.lfs.2024.122514
  • PMID/PMCID: 38395386

Research overview

We aim to determine the effects and mechanisms of gestational diabetes mellitus (GDM) hypermetabolic stress on glucose homeostasis in pregnant mice and functional maturation of the islets of their offspring. These findings provide preliminary insights into the mechanisms underlying the high incidence of diabetes in the offspring of mothers with GDM.

Key findings

GDM exosomes induced remarkable oral glucose intolerance, hyperinsulinemia, and metabolic inflammation in pregnant mice.

The islets of GDM offspring exhibited high insulin, glucagon, PC1/3, PDX1, and p-S6 expression at and after birth, and activation of the local GLP-1/GLP-1R axis.

The functional maturation of normal-offspring islets did not commence until after birth, while it was activated prior to birth in GDM offspring, seriously disrupting the whole process.

GDM exosomes activated the GLP-1/GLP-1R axis between α and β cells, and stimulated functional maturation of β cells via the Akt-mTORC1-pS6 pathway.

Study design

Exosomes were extracted from the umbilical vein blood of individuals with or without GDM for administration to pregnant mice.

The blood glucose, serum insulin, glycosylated hemoglobin, and lipopolysaccharide levels were measured in pregnant mice.

The expression and localization of insulin, glucagon, PC1/3, PDX1, and p-S6 in the islets of neonatal rats were continuously monitored using immunofluorescence to evaluate their functional status.

Echo Biotech Role

Echo Biotech contributed EV isolation and purification, EV characterization; the study also used or cited Exosupur®.

Related platforms: Exoomics®, Research Reagents & Tools

Related services and capabilities: Biofluid EV Isolation & Purification, EV Basic Characterization (TEM/NTA/WB), Research Reagent / Product Supply

Related products or reagents: Exosupur® EV Isolation/Purification Kit

References

Original publication: Human gestational diabetes mellitus-derived exosomes impair glucose homeostasis in pregnant mice and stimulate functional maturation of offspring-islets Life Sci. 2024. DOI: 10.1016/j.lfs.2024.122514. PMID/PMCID: 38395386.