| First Author | Panzer JK | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 11 | Pages | 111792 |
| PubMed ID | 36516761 | Mgi Jnum | J:354536 |
| Mgi Id | MGI:7424707 | Doi | 10.1016/j.celrep.2022.111792 |
| Citation | Panzer JK, et al. (2022) Restoring glutamate receptor signaling in pancreatic alpha cells rescues glucagon responses in type 1 diabetes. Cell Rep 41(11):111792 |
| abstractText | Glucagon secretion from pancreatic alpha cells is crucial to prevent hypoglycemia. People with type 1 diabetes lose this glucoregulatory mechanism and are susceptible to dangerous hypoglycemia for reasons still unclear. Here we determine that alpha cells in living pancreas slices from donors with type 1 diabetes do not mount an adequate glucagon response and cannot activate the positive autocrine feedback mediated by AMPA/kainate glutamate receptors. This feedback is required to elicit full glucagon responses in the healthy state. Reactivating residual AMPA/kainate receptor function with positive allosteric modulators restores glucagon secretion in human slices from donors with type 1 diabetes as well as glucose counterregulation in non-obese diabetic mice. Our study thus identifies a defect in autocrine signaling that contributes to alpha cell failure. The use of positive allosteric modulators of AMPA/kainate receptors overcomes this deficiency and prevents hypoglycemia, an effect that could be used to improve the management of diabetes. |
