| First Author | Supale S | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 10 | Pages | 3488-99 |
| PubMed ID | 23863811 | Mgi Jnum | J:208944 |
| Mgi Id | MGI:5565419 | Doi | 10.2337/db13-0152 |
| Citation | Supale S, et al. (2013) Loss of prohibitin induces mitochondrial damages altering beta-cell function and survival and is responsible for gradual diabetes development. Diabetes 62(10):3488-99 |
| abstractText | Prohibitins are highly conserved proteins mainly implicated in the maintenance of mitochondrial function and architecture. Their dysfunctions are associated with aging, cancer, obesity, and inflammation. However, their possible role in pancreatic beta-cells remains unknown. The current study documents the expression of prohibitins in human and rodent islets and their key role for beta-cell function and survival. Ablation of Phb2 in mouse beta-cells sequentially resulted in impairment of mitochondrial function and insulin secretion, loss of beta-cells, progressive alteration of glucose homeostasis, and, ultimately, severe diabetes. Remarkably, these events progressed over a 3-week period of time after weaning. Defective insulin supply in beta-Phb2(-/-) mice was contributed by both beta-cell dysfunction and apoptosis, temporarily compensated by increased beta-cell proliferation. At the molecular level, we observed that deletion of Phb2 caused mitochondrial abnormalities, including reduction of mitochondrial DNA copy number and respiratory chain complex IV levels, altered mitochondrial activity, cleavage of L-optic atrophy 1, and mitochondrial fragmentation. Overall, our data demonstrate that Phb2 is essential for metabolic activation of mitochondria and, as a consequence, for function and survival of beta-cells. |
