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Title

Loss of prohibitin induces mitochondrial damages altering β-cell function and survival and is responsible for gradual diabetes development

Authors
Merkwirth, Carsten
Gjinovci, Asllan
Langer, Thomas
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Published in Diabetes. 2013, vol. 62, no. 10, p. 3488-99
Abstract 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 β-cells remains unknown. The current study documents the expression of prohibitins in human and rodent islets and their key role for β-cell function and survival. Ablation of Phb2 in mouse β-cells sequentially resulted in impairment of mitochondrial function and insulin secretion, loss of β-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 β-Phb2(-/-) mice was contributed by both β-cell dysfunction and apoptosis, temporarily compensated by increased β-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 β-cells.
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PMID: 23863811
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Article (Published version) (1.8 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research groups Types cellulaires pancréatiques pendant l'ontogénèse (522)
Mitochondries et sécrétion d'insuline (671)
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SUPALE, Sachin et al. Loss of prohibitin induces mitochondrial damages altering β-cell function and survival and is responsible for gradual diabetes development. In: Diabetes, 2013, vol. 62, n° 10, p. 3488-99. https://archive-ouverte.unige.ch/unige:32131

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Deposited on : 2013-12-16

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