Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function.
Haixia XuXiao DuJia XuYu ZhangYan TianGeng LiuXiuxuan WangMeilin MaWenya DuYu LiuLunzhi DaiWendong HuangNanwei TongYuquan WeiXianghui FuPublished in: PLoS biology (2020)
Type 2 diabetes (T2D) is characterized by insulin resistance along with pancreatic β cell failure. β cell factors are traditionally thought to control glucose homeostasis by modulating insulin levels, not insulin sensitivity. Exosomes are emerging as new regulators of intercellular communication. However, the role of β-cell-derived exosomes in metabolic homeostasis is poorly understood. Here, we report that microRNA-26a (miR-26a) in β cells not only modulates insulin secretion and β cell replication in an autocrine manner but also regulates peripheral insulin sensitivity in a paracrine manner through circulating exosomes. MiR-26a is reduced in serum exosomes of overweight humans and is inversely correlated with clinical features of T2D. Moreover, miR-26a is down-regulated in serum exosomes and islets of obese mice. Using miR-26a knockin and knockout mouse models, we showed that miR-26a in β cells alleviates obesity-induced insulin resistance and hyperinsulinemia. Mechanistically, miR-26a in β cells enhances peripheral insulin sensitivity via exosomes. Meanwhile, miR-26a prevents hyperinsulinemia through targeting several critical regulators of insulin secretion and β cell proliferation. These findings provide a new paradigm for the far-reaching systemic functions of β cells and offer opportunities for the treatment of T2D.
Keyphrases
- cell proliferation
- type diabetes
- long non coding rna
- insulin resistance
- induced apoptosis
- mesenchymal stem cells
- long noncoding rna
- stem cells
- cell cycle arrest
- cell cycle
- cell therapy
- pi k akt
- metabolic syndrome
- mouse model
- signaling pathway
- adipose tissue
- glycemic control
- high fat diet
- oxidative stress
- cardiovascular disease
- endoplasmic reticulum stress
- skeletal muscle
- endothelial cells
- blood pressure
- body mass index
- drug delivery
- cancer therapy
- drug induced
- chemotherapy induced