| First Author | Traub S | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 13 | Pages | 3192-3203 |
| PubMed ID | 28355570 | Mgi Jnum | J:251808 |
| Mgi Id | MGI:6103643 | Doi | 10.1016/j.celrep.2017.03.005 |
| Citation | Traub S, et al. (2017) Pancreatic alpha Cell-Derived Glucagon-Related Peptides Are Required for beta Cell Adaptation and Glucose Homeostasis. Cell Rep 18(13):3192-3203 |
| abstractText | Pancreatic alpha cells may process proglucagon not only to glucagon but also to glucagon-like peptide-1 (GLP-1). However, the biological relevance of paracrine GLP-1 for beta cell function remains unclear. We studied effects of locally derived insulin secretagogues on beta cell function and glucose homeostasis using mice with alpha cell ablation and with alpha cell-specific GLP-1 deficiency. Normally, intestinal GLP-1 compensates for the lack of alpha cell-derived GLP-1. However, upon aging and metabolic stress, glucose tolerance is impaired. This was partly rescued with the DPP-4 inhibitor sitagliptin, but not with glucagon administration. In isolated islets from these mice, glucose-stimulated insulin secretion was heavily impaired and exogenous GLP-1 or glucagon rescued insulin secretion. These data highlight the importance of alpha cell-derived GLP-1 for glucose homeostasis during metabolic stress and may impact on the clinical use of systemic GLP-1 agonists versus stabilizing local alpha cell-derived GLP-1 by DPP-4 inhibitors in type 2 diabetes. |
