| First Author | Pydi SP | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 23 | Pages | eaaz1341 |
| PubMed ID | 32537493 | Mgi Jnum | J:343902 |
| Mgi Id | MGI:7485906 | Doi | 10.1126/sciadv.aaz1341 |
| Citation | Pydi SP, et al. (2020) Beneficial metabolic role of beta-arrestin-1 expressed by AgRP neurons. Sci Adv 6(23):eaaz1341 |
| abstractText | beta-Arrestin-1 and beta-arrestin-2 have emerged as important signaling molecules that modulate glucose fluxes in several peripheral tissues. The potential roles of neuronally expressed beta-arrestins in regulating glucose homeostasis remain unknown. We here report that mice lacking beta-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 beta-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. |
