The mitochondrial Ca2+uniporter MCU is required for normal glucose-stimulated insulin secretionin vitroandin vivo
| Autor: | Paul M. W. French, Guy A. Rutter, Isabelle Leclerc, Francesca Semplici, Eleni Georgiadou, Rosario Rizzuto, David A. Jacobson, Matthew T. Dickerson, Aida Martinez-Sanchez, da Silva Xavier G, Samuel P. X. Davis, Timothy J. Pullen, Elizabeth Haythorne, Matthew C. Cane, James McGinty, Livia Lopez-Noriega |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
medicine.medical_specialty Chemistry Insulin medicine.medical_treatment 030209 endocrinology & metabolism Mitochondrion In vitro 03 medical and health sciences Cytosol 0302 clinical medicine Endocrinology In vivo Internal medicine medicine Beta (finance) Uniporter Inner mitochondrial membrane 030304 developmental biology |
| Popis: | Mitochondrial oxidative metabolism is central to glucose-stimulated insulin secretion (GSIS). Whether Ca2+uptake into pancreatic β-cell mitochondria potentiates or antagonises this process is still a matter of debate. Although the mitochondrial importer (MCU) complex is thought to represent the main route for Ca2+transport across the inner mitochondrial membrane, its role in β-cells has not previously been examinedin vivo. Here, we inactivated the pore-forming subunit MCUa (MCU) selectively in the β-cell in mice usingIns1Cre-mediated recombination. Glucose-stimulated mitochondrial Ca2+accumulation, ATP production and insulin secretion were strongly (pMCUnull animals (βMCU-KO)in vitro. Interestingly, cytosolic Ca2+concentrations increased (pin vivoinsulin secretion at 5 (p2+uptake in pancreatic β-cells and is required for normal GSIS. The apparent compensatory mechanisms which maintain glucose tolerance in βMCU-KO mice remain to be established. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|