| First Author | Abe H | Year | 2013 |
| Journal | Endocrinology | Volume | 154 |
| Issue | 12 | Pages | 4512-24 |
| PubMed ID | 24105478 | Mgi Jnum | J:205147 |
| Mgi Id | MGI:5544155 | Doi | 10.1210/en.2013-1578 |
| Citation | Abe H, et al. (2013) Exendin-4 improves beta-cell function in autophagy-deficient beta-cells. Endocrinology 154(12):4512-24 |
| abstractText | Autophagy is cellular machinery for maintenance of beta-cell function and mass. The implication of autophagy failure in beta-cells on the pathophysiology of type 2 diabetes and its relation to the effect of treatment of diabetes remains elusive. Here, we found increased expression of p62 in islets of db/db mice and patients with type 2 diabetes mellitus. Treatment with exendin-4, a glucagon like peptide-1 receptor agonist, improved glucose tolerance in db/db mice without significant changes in p62 expression in beta-cells. Also in beta-cell-specific Atg7-deficient mice, exendin-4 efficiently improved blood glucose level and glucose tolerance mainly by enhanced insulin secretion. In addition, we found that exendin-4 reduced apoptotic cell death and increased proliferating cells in the Atg7-deficient islets, and that exendin-4 counteracted thapsigargin-induced cell death of isolated islets augmented by autophagy deficiency. Our results suggest the potential involvement of reduced autophagy in beta-cell dysfunction in type 2 diabetes. Without altering the autophagic state in beta-cells, exendin-4 improves glucose tolerance associated with autophagy deficiency in beta-cells. This is mainly achieved through augmentation of insulin secretion. In addition, exendin-4 prevents apoptosis and increases the proliferation of beta-cells associated with autophagy deficiency, also without altering the autophagic machinery in beta-cells. |
