Hypothalamic miR-1983 Targets Insulin Receptor β and the Insulin-mediated miR-1983 Increase Is Blocked by Metformin
| Autor: | Jennifer A Chalmers, Prasad S Dalvi, Neruja Loganathan, Emma K McIlwraith, Leigh Wellhauser, Anaies Nazarians-Armavil, Judith A Eversley, Haneesha Mohan, Priska Stahel, Satya Dash, Michael B Wheeler, Denise D Belsham |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Hypothalamus 030209 endocrinology & metabolism Cell Line Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Animals Humans Hypoglycemic Agents Insulin Obesity Cells Cultured 030304 developmental biology Neurons 0303 health sciences Gene Expression Profiling Middle Aged Metformin Receptor Insulin 3. Good health MicroRNAs Gene Expression Regulation Female Insulin Resistance Research Article |
| Zdroj: | Endocrinology |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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