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Long non-coding RNA GAS5 binds to miR-137 and regulates Nrf2 to ameliorate insulin resistance in adipose tissue in gestational diabetes mellitus.

Created on 05 Sep 2026

Authors

Yuanyuan Guo, Jingru Jiao, Xian Zheng

Published in

Diabetic medicine : a journal of the British Diabetic Association. Pages e70451. Sep 04, 2026. Epub Sep 04, 2026.

Abstract

This study aimed to explore whether GAS5 improves gestational diabetes mellitus (GDM)-associated insulin resistance (IR) via the miR-137/Nrf2 axis, thereby elucidating a potential novel mechanism underlying GDM pathogenesis.
GAS5 and Nrf2 expression was compared between GDM patients and normal glucose tolerance pregnant women, and their correlations with IR and lipid metabolism indexes were analysed. A dexamethasone-induced adipocyte IR model was constructed. Cellular functional changes in glucose uptake, fatty acid metabolism and lipid deposition were detected following GAS5 overexpression and miR-137/Nrf2 intervention to validate the regulatory mechanism.
GAS5 and Nrf2 were markedly decreased in GDM peripheral blood and closely correlated with IR and lipid metabolic phenotypes. GAS5 overexpression increased adipocyte glucose uptake and alleviated IR and lipid disorders. Mechanistically, GAS5 directly binds and inhibits miR-137 to upregulate Nrf2. Rescue assays showed that miR-137 elevation or Nrf2 suppression partially reversed the protective effects of GAS5, reducing glucose uptake and fatty acid oxidation while increasing free fatty acid release and lipid accumulation.
GAS5 and Nrf2 are lowly expressed in GDM patients. This study demonstrates that GAS5 ameliorates adipocyte IR and lipid metabolic dysfunction by sponging miR-137 to elevate Nrf2 expression, providing a novel mechanistic insight for GDM.

PMID:
42698187
Bibliographic data and abstract were imported from PubMed on 05 Sep 2026.

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