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miR-486-5p-rich extracellular vesicles derived from patients with olanzapine-induced insulin resistance negatively

Chuyue Tu1, Qian Wu1, Jing Wang1

  • 1Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Biochemical Pharmacology
|May 24, 2024
PubMed

Insights

Extracellular vesicles (EVs) from patients treated with olanzapine can cause insulin resistance in rats and adipocytes. Specific microRNAs (miRNAs) within these EVs, like miR-486-5p, contribute to these metabolic changes.

Area of Science:

  • Biochemistry
  • Metabolic Disorders
  • Pharmacology

Background:

  • Olanzapine treatment can lead to glucometabolic disorders, limiting its clinical use.
  • MicroRNAs (miRNAs) within extracellular vesicles (EVs) are potential biomarkers for metabolic disorders.

Purpose of the Study:

  • To investigate the role of plasma EVs in interindividual differences in olanzapine-induced insulin resistance (IR).
  • To identify specific miRNAs in EVs associated with olanzapine-induced IR.
  • To explore the underlying mechanisms of EV-mediated metabolic dysfunction.

Main Methods:

  • Plasma EVs were isolated from 81 patients undergoing olanzapine treatment and injected into rats.
  • High-throughput sequencing was used for miRNA profiling to compare susceptible and non-susceptible groups.
  • In vitro experiments involved coculturing adipocytes with antagomir-treated EVs.

Main Results:

  • Individual insulin sensitivity varied among patients and in olanzapine-treated rats.
  • EVs from olanzapine-induced IR patients induced metabolic abnormalities in rats and adipocytes via the AKT-GLUT4 pathway.
  • Distinct miRNA profiles were observed in EVs based on IR susceptibility, with miR-486-5p identified as a key player.

Conclusions:

  • Plasma EVs play a significant role in the variability of olanzapine-induced insulin sensitivity.
  • Circulating EVs can transmit metabolic dysfunction, highlighting their potential as biomarkers and therapeutic targets.
  • miR-486-5p is implicated in the development of olanzapine-induced insulin resistance.
Keywords:
AdipocyteCirculating extracellular vesiclesInsulin resistanceOlanzapinemiRNA

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