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IL-10 Enhances the Inhibitory Effect of Adipose-Derived Stromal Cells on Insulin Resistance/Liver Gluconeogenesis by Treg Cell Induction.
Lai, Hsiao-Chi; Chen, Pei-Hsuan; Tang, Chia-Hua; Chen, Lee-Wei.
Afiliación
  • Lai HC; Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
  • Chen PH; Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
  • Tang CH; Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
  • Chen LW; Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
Int J Mol Sci ; 25(15)2024 Jul 25.
Article en En | MEDLINE | ID: mdl-39125659
ABSTRACT
The modulation of cellular phenotypes within adipose tissue provides a potential means for therapeutic intervention for diabetes. Endogenous interleukin-10 (IL-10) protects against diet-induced insulin resistance. We examined the effects and mechanisms of action of IL-10-treated adipose-derived stromal cells on diabetes-induced insulin resistance and liver gluconeogenesis. We harvested stromal vascular fractions (SVFs) from the adipose tissue of diabetic (Leprdb/db) mice and treated them with IL-10 in vitro. SVFs treated with 10 or 100 ng of IL-10 were injected into the inguinal adipose tissue of Leprdb/db mice. IL-10 treatment suppressed the mRNA expression of IL-6, IL-33, CCL2, TNF-α, and IL-1ß. Additionally, it suppressed the protein expression of IL-6, pmTOR, pJNK, and pNF-κB but enhanced Foxp3 mRNA expression in SVFs from diabetic mice. Meanwhile, IL-10 treatment repressed CCL2 and PDGFRα expression in adipose tissue macrophages (ATMs) and IL-6 expression in non-ATMs but increased the Foxp3 and IL-10 mRNA expression of ATMs from diabetic mice. Injection of IL-10-treated SVFs decreased the IL-6, IL-33, CCL2, IL-1ß, and CCL2 but enhanced the Foxp3 and IL-10 mRNA expression of adipose tissue from Leprdb/db mice. Furthermore, injection of IL-10-treated SVFs increased CD4+ regulatory T cells (Tregs) in SVFs and adipose IL-10 levels and suppressed plasma adiponectin levels and DPP4 activity in diabetic mice. Injection of IL-10-treated SVFs decreased hepatic G6PC and PCK1 mRNA expression and increased Akt activation, STAT3 phosphorylation in the liver, and glucose tolerance in diabetic mice. Our data suggest that IL-10 treatment decreases inflammation in adipose SVFs of diabetic mice. Injection of IL-10-treated SVFs into the adipose tissue decreased diabetes-induced gluconeogenesis gene expression, DPP4 activity, and insulin resistance by enhancing Treg cells in diabetic mice. These data suggest that IL-10-treated adipose stromal vascular cells could be a promising therapeutic strategy for diabetes mellitus.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Tejido Adiposo / Interleucina-10 / Células del Estroma / Linfocitos T Reguladores / Gluconeogénesis / Hígado Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Taiwán

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Resistencia a la Insulina / Tejido Adiposo / Interleucina-10 / Células del Estroma / Linfocitos T Reguladores / Gluconeogénesis / Hígado Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Taiwán