| First Author | Li R | Year | 2020 |
| Journal | Diabetes | Volume | 69 |
| Issue | 7 | Pages | 1463-1475 |
| PubMed ID | 32332156 | Mgi Jnum | J:293273 |
| Mgi Id | MGI:6445785 | Doi | 10.2337/db19-0909 |
| Citation | Li R, et al. (2020) Lactogens Reduce Endoplasmic Reticulum Stress-Induced Rodent and Human beta-Cell Death and Diabetes Incidence in Akita Mice. Diabetes 69(7):1463-1475 |
| abstractText | Diabetes occurs due to a loss of functional beta-cells, resulting from beta-cell death and dysfunction. Lactogens protect rodent and human beta-cells in vitro and in vivo against triggers of beta-cell cytotoxicity relevant to diabetes, many of which converge onto a common pathway of endoplasmic reticulum (ER) stress. However, whether lactogens modulate the ER stress pathway is unknown. This study examines whether lactogens can protect beta-cells against ER stress and mitigate diabetes incidence in Akita (Ak) mice, a rodent model of ER stress-induced diabetes, akin to neonatal diabetes in humans. We show that lactogens protect INS-1 cells, primary rodent and human beta-cells in vitro against two distinct ER stressors, tunicamycin and thapsigargin, through activation of the JAK2/STAT5 pathway. Lactogens mitigate expression of proapoptotic molecules in the ER stress pathway that are induced by chronic ER stress in INS-1 cells and rodent islets. Transgenic expression of placental lactogen in beta-cells of Ak mice drastically reduces the severe hyperglycemia, diabetes incidence, hypoinsulinemia, beta-cell death, and loss of beta-cell mass observed in Ak littermates. These are the first studies in any cell type demonstrating that lactogens modulate the ER stress pathway, causing enhanced beta-cell survival and reduced diabetes incidence in the face of chronic ER stress. |
