Beneficial metabolic role of β-arrestin-1 expressed by AgRP neurons
| Autor: | Hale Ergin Egritag, Luiz Felipe Barella, Zhenzhong Cui, Sai Prasad Pydi, Douglas J. Oberlin, Oksana Gavrilova, Gary J. Schwartz, Christoph Buettner, Kevin W. Williams, Nikhil M. Urs, Jonathan Pham, Jürgen Wess, Zhenyan He, Yinghong Cui |
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| Rok vydání: | 2019 |
| Předmět: |
Cell signaling
genetic structures Physiology Adipose tissue 030209 endocrinology & metabolism Diseases and Disorders Biology Impaired glucose tolerance 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Glucose homeostasis Lipolysis Research Articles 030304 developmental biology 0303 health sciences Multidisciplinary digestive oral and skin physiology SciAdv r-articles Hyperpolarization (biology) medicine.disease Phenotype Cell biology Electrophysiology nervous system sense organs Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | This study suggests that agents able to enhance the activity of β-arrestin-1 in AgRP neurons may be useful as antidiabetic drugs. β-Arrestin-1 and β-arrestin-2 have emerged as important signaling molecules that modulate glucose fluxes in several peripheral tissues. The potential roles of neuronally expressed β-arrestins in regulating glucose homeostasis remain unknown. We here report that mice lacking β-arrestin-1 (barr1) selectively in AgRP neurons displayed impaired glucose tolerance and insulin sensitivity when consuming an obesogenic diet, while mice overexpressing barr1 selectively in AgRP neurons were protected against obesity-associated metabolic impairments. Additional physiological, biochemical, and electrophysiological data indicated that the presence of barr1 is essential for insulin-mediated hyperpolarization of AgRP neurons. As a result, barr1 expressed by AgRP neurons regulates efferent neuronal pathways that suppress hepatic glucose production and promote lipolysis in adipose tissue. Mice lacking β-arrestin-2 (barr2) selectively in AgRP neurons showed no substantial metabolic phenotypes. Our data suggest that agents able to enhance the activity of barr1 in AgRP neurons may prove beneficial as antidiabetic drugs. |
| Databáze: | OpenAIRE |
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