Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA.
Sirolimus (rapamycin) is an immunosuppressive drug used in transplantation. One of its major side effects is the increased risk of diabetes mellitus; however, the exact mechanisms underlying such association have not been elucidated. Here we show that sirolimus impairs glucose-stimulated insulin secretion both in human and murine pancreatic islets and in clonal β cells in a dose- and time-dependent manner. Importantly, we demonstrate that sirolimus markedly depletes calcium (Ca) content in the endoplasmic reticulum and significantly decreases glucose-stimulated mitochondrial Ca uptake. Crucially, the reduced mitochondrial Ca uptake is mirrored by a significant impairment in mitochondrial respiration. Taken together, our findings indicate that sirolimus causes depletion of intracellular Ca stores and alters mitochondrial fitness, eventually leading to decreased insulin release. Our results provide a novel molecular mechanism underlying the increased incidence of diabetes mellitus in patients treated with this drug.
We have submitted your request - we will update you on status within the next 24 hours.
Sign up for further access to Scientific Publications and Authors!
What are PubFacts Points?
PubFacts points are rewards to PubFacts members, which allow you to better promote your profile and articles throughout PubFacts.com
How do I earn PubFacts Points?
Each member is given 50 PubFacts points upon signing up. You can earn additional points by completing 100% of your profile, creating and participating in discussions, and sharing other members research.
What can I do with PubFacts Points?
Currently, you can use PubFacts Points to promote and increase readership of your articles.