| First Author | Liu L | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 5129 |
| PubMed ID | 38879678 | Mgi Jnum | J:349919 |
| Mgi Id | MGI:7659986 | Doi | 10.1038/s41467-024-49537-x |
| Citation | Liu L, et al. (2024) Intra-islet alpha-cell Gs signaling promotes glucagon release. Nat Commun 15(1):5129 |
| abstractText | Glucagon, a hormone released from pancreatic alpha-cells, is critical for maintaining euglycemia and plays a key role in the pathophysiology of diabetes. To stimulate the development of new classes of therapeutic agents targeting glucagon release, key alpha-cell signaling pathways that regulate glucagon secretion need to be identified. Here, we focused on the potential importance of alpha-cell G(s) signaling on modulating alpha-cell function. Studies with alpha-cell-specific mouse models showed that activation of alpha-cell G(s) signaling causes a marked increase in glucagon secretion. We also found that intra-islet adenosine plays an unexpected autocrine/paracrine role in promoting glucagon release via activation of alpha-cell G(s)-coupled A(2A) adenosine receptors. Studies with alpha-cell-specific Galpha(s) knockout mice showed that alpha-cell G(s) also plays an essential role in stimulating the activity of the Gcg gene, thus ensuring proper islet glucagon content. Our data suggest that alpha-cell enriched G(s)-coupled receptors represent potential targets for modulating alpha-cell function for therapeutic purposes. |
