期刊
ENDOCRINOLOGY
卷 163, 期 1, 页码 -出版社
ENDOCRINE SOC
DOI: 10.1210/endocr/bqab241
关键词
microRNA; insulin resistance; obesity; hyperinsulinemia; hypothalamus; NPY neuron
资金
- Canadian Institute for Health Research (CIHR)
- CIHR Foundation
- Diabetes Action Canada Postdoctoral Fellowship
This study identified a unique miRNA (miR-1983) that is upregulated in the hypothalamus and can serve as a biomarker for cellular insulin resistance. The levels of miR-1983 in human blood serum correlate with insulin resistance.
MicroRNAs (miRNAs) expressed in the hypothalamus are capable of regulating energy balance and peripheral metabolism by inhibiting translation of target messenger RNAs (mRNAs). Hypothalamic insulin resistance is known to precede that in the periphery, thus a critical unanswered question is whether central insulin resistance creates a specific hypothalamic miRNA signature that can be identified and targeted. Here we show that miR-1983, a unique miRNA, is upregulated in vitro in 2 insulin-resistant immortalized hypothalamic neuronal neuropeptide Y-expressing models, and in vivo in hyperinsulinemic mice, with a concomitant decrease of insulin receptor beta subunit protein, a target of miR-1983. Importantly, we demonstrate that miR-1983 is detectable in human blood serum and that its levels significantly correlate with blood insulin and the homeostatic model assessment of insulin resistance. Levels of miR-1983 are normalized with metformin exposure in mouse hypothalamic neuronal cell culture. Our findings provide evidence for miR-1983 as a unique biomarker of cellular insulin resistance, and a potential therapeutic target for prevention of human metabolic disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据