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Raptor regulates functional maturation of murine beta cells
Diabetes is associated with beta cell mass loss and islet dysfunctions. mTORC1 regulates beta cell survival, proliferation and function in physiological and pathological conditions, such as pregnancy and pancreatectomy. Here we show that deletion of Raptor , which is an essential component of mTORC1...
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Published in: | Nature communications 2017-06, Vol.8 (1), p.15755-15755, Article 15755 |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Diabetes is associated with beta cell mass loss and islet dysfunctions. mTORC1 regulates beta cell survival, proliferation and function in physiological and pathological conditions, such as pregnancy and pancreatectomy. Here we show that deletion of
Raptor
, which is an essential component of mTORC1, in insulin-expressing cells promotes hypoinsulinemia and glucose intolerance.
Raptor
-deficient beta cells display reduced glucose responsiveness and exhibit a glucose metabolic profile resembling fetal beta cells. Knockout islets have decreased expression of key factors of functional maturation and upregulation of neonatal markers and beta cell disallowed genes, resulting in loss of functional maturity. Mechanistically,
Raptor
-deficient beta cells show reduced expression of DNA-methyltransferase 3a and altered patterns of DNA methylation at loci that are involved in the repression of disallowed genes. The present findings highlight a novel role of mTORC1 as a core mechanism governing postnatal beta cell maturation and physiologic beta cell mass during adulthood.
mTORC1 regulates beta cell survival, function and adaptation to physiologic and pathological stimuli. Here Ni
et al
. demonstrate that that deficiency of Raptor, a component of mTORC1 complex, impairs insulin secretion and glucose tolerance in mice by affecting maturation of beta cells during the postnatal period. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms15755 |