PDF(Pubmed)
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-1β. 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-1β, 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.
摘要：
脂肪组织内细胞表型的调节为糖尿病的治疗干预提供了潜在的手段。内源性白细胞介素-10（IL-10）保护免受饮食诱导的胰岛素抵抗。我们研究了IL-10处理的脂肪基质细胞对糖尿病诱导的胰岛素抵抗和肝脏糖异生的作用和机制。我们从糖尿病（Leprdb/db）小鼠的脂肪组织中收获基质血管部分（SVF），并在体外用IL-10处理。将用10或100ngIL-10处理的SVF注射到Leprdb/db小鼠的腹股沟脂肪组织中。IL-10处理抑制IL-6、IL-33、CCL2、TNF-α的mRNA表达,和IL-1β。此外,它抑制了IL-6，pmTOR，pJNK,和pNF-κB，但增强了糖尿病小鼠SVF中Foxp3mRNA的表达。同时,IL-10治疗抑制了脂肪组织巨噬细胞（ATM）中的CCL2和PDGFRα表达以及非ATM中的IL-6表达，但增加了糖尿病小鼠ATM的Foxp3和IL-10mRNA表达。注射IL-10处理的SVFs降低了IL-6，IL-33，CCL2，IL-1β，但增强了Leprdb/db小鼠脂肪组织的Foxp3和IL-10mRNA表达。此外，在糖尿病小鼠中,注射IL-10处理的SVF可增加SVF中的CD4+调节性T细胞(Tregs)和脂肪IL-10水平,并抑制血浆脂联素水平和DPP4活性。注射IL-10处理的SVFs降低肝脏G6PC和PCK1mRNA表达并增加Akt活化,肝脏中的STAT3磷酸化，和糖尿病小鼠的葡萄糖耐量。我们的数据表明，IL-10治疗可降低糖尿病小鼠脂肪SVF的炎症。将IL-10处理的SVFs注射到脂肪组织中降低糖尿病诱导的糖异生基因表达,DPP4活性，通过增强糖尿病小鼠的Treg细胞和胰岛素抵抗。这些数据表明，IL-10处理的脂肪基质血管细胞可能是糖尿病的有希望的治疗策略。
