1α,25(OH) 2 D 3 ameliorates insulin resistance by alleviating γδ T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background: Chronic inflammation caused by immune cells is the central link between obesity and insulin resistance. Targeting the inflammatory process is a highly promising method for reversing systemic insulin resistance. Methods: Blood samples were prospectively collected from 68 patients with type 2 diabetes. C57BL/6J mice were fed either a high-fat diet (HFD) or normal chow (NC). We performed phenotypical and functional analyses of immune cells using flow cytometry. Vitamin D receptor (VDR) knockout γδ T cells were constructed using Cas9-gRNA targeted approaches to identify 1α,25(OH) 2 D 3 /VDR signaling pathway-mediated transcriptional regulation of fructose-1,6-bisphosphatase (FBP1) in γδ T cells. Results: Serum vitamin D deficiency aggravates inflammation in circulating γδ T cells in type 2 diabetes patients. We defined a critical role for 1α,25(OH) 2 D 3 in regulating glycolysis metabolism, protecting against inflammation, and alleviating insulin resistance. Mechanistically, 1α,25(OH) 2 D 3 -VDR promoted FBP1 expression to suppress glycolysis in γδ T cells, thereby inhibiting Akt/p38 MAPK phosphorylation and reducing inflammatory cytokine production. Notably, therapeutic administration of 1α,25(OH) 2 D 3 restrained inflammation in γδ T cells and ameliorated systemic insulin resistance in obese mice. Conclusions: Collectively, these findings show that 1α,25(OH) 2 D 3 pla

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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