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Pancreatic ? cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving ? cell function.

ABSTRACT: Type 2 diabetes (T2D) is characterized by insulin resistance along with pancreatic ? cell failure. ? 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 ?-cell-derived exosomes in metabolic homeostasis is poorly understood. Here, we report that microRNA-26a (miR-26a) in ? cells not only modulates insulin secretion and ? 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 ? cells alleviates obesity-induced insulin resistance and hyperinsulinemia. Mechanistically, miR-26a in ? cells enhances peripheral insulin sensitivity via exosomes. Meanwhile, miR-26a prevents hyperinsulinemia through targeting several critical regulators of insulin secretion and ? cell proliferation. These findings provide a new paradigm for the far-reaching systemic functions of ? cells and offer opportunities for the treatment of T2D.

SUBMITTER: Xu H

PROVIDER: S-EPMC7058362 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function.

Xu Haixia H Du Xiao X Xu Jia J Zhang Yu Y Tian Yan Y Liu Geng G Wang Xiuxuan X Ma Meilin M Du Wenya W Liu Yu Y Dai Lunzhi L Huang Wendong W Tong Nanwei N Wei Yuquan Y Fu Xianghui X

PLoS biology 20200224 2

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 replica ...[more]

PMID: 32092075

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Dataset Information

Pancreatic ? cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving ? cell function.

Publications

Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function.

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