Therapeutic effects of 1,25-dihydroxyvitamin D₃ with astragalus polysaccharide on insulin resistance in gestational diabetes mellitus rat models.

Authors

Shuqi Yan, Haoyan Ma, Wenjian Li, Jiayuan Qu, Ming Wei, Chong Tan, Qizheng Pan, Shuping Ren, Yuhong Wang

Published in

Molecular biology reports. Volume 53. Issue 1. Aug 29, 2026. Epub Aug 29, 2026.

Abstract

Approximately 9 to 26% of pregnant individuals develop gestational diabetes mellitus (GDM), for which insulin resistance is a key driver. 1,25-dihydroxyvitamin D (1,25(OH)₂D₃) and astragalus polysaccharide (APS) can each alleviate insulin resistance, yet their combined mechanisms remain poorly elucidated.
Diabetic rats were induced by high-fat diet and low-dose streptozotocin in Sprague-Dawley rats, then treated with 1,25(OH)₂D₃, APS, or both for two weeks. Serum glucose, insulin, and lipid profiles were measured. In the liver, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) activity, liver function markers, and protein expression of vitamin D receptor (VDR), insulin signaling, PI3K/AKT/FOXO1, gluconeogenesis, and lipid metabolism pathways were assessed. Co-immunoprecipitation was also performed to examine VDR-PI3K p85 interaction.
In GDM rats, combined 1,25(OH)₂D₃ and APS intervention significantly reduced the serum levels of glucose, aspartate aminotransferase, alanine aminotransferase, free fatty acid, triglyceride and apolipoprotein B, and homeostatic model assessment of insulin resistance(p < 0.05). The combination decreased hepatic ROS and MDA levels, increased hepatic SOD activity, upregulated VDR and cytochrome P450 2R1 mRNA levels, and increased the protein expression levels of VDR, insulin receptor, insulin receptor substrate 1, glucose transporter 2, PI3K, AKT, pAKT and the pAKT/AKT ratio (p < 0.05). It also suppressed the protein expression levels of FOXO1, PEPCK, G6pase and SREBP1C, and increased PPARγ levels (p < 0.05). Co-immunoprecipitation assay confirmed a potential interaction between VDR and PI3K p85 in liver tissues.
Combined 1,25(OH)₂D₃ and APS alleviated insulin resistance and metabolic disorders in GDM rats, possibly via VDR upregulation, oxidative stress attenuation, and PI3K/AKT/FOXO1 signaling modulation.

PMID:
42667463
Bibliographic data and abstract were imported from PubMed on 30 Aug 2026.

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