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Hypothalamic miR-1983 Targets Insulin Receptor β and the Insulin-mediated miR-1983 Increase Is Blocked by Metformin

Authors :
Chalmers, Jennifer A
Dalvi, Prasad S
Loganathan, Neruja
McIlwraith, Emma K
Wellhauser, Leigh
Nazarians-Armavil, Anaies
Eversley, Judith A
Mohan, Haneesha
Stahel, Priska
Dash, Satya
Wheeler, Michael B
Belsham, Denise D
Source :
Endocrinology; January 2022, Vol. 163 Issue: 1
Publication Year :
2022

Abstract

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 β 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.

Details

Language :
English
ISSN :
00137227 and 19457170
Volume :
163
Issue :
1
Database :
Supplemental Index
Journal :
Endocrinology
Publication Type :
Periodical
Accession number :
ejs60751605
Full Text :
https://doi.org/10.1210/endocr/bqab241