Raptor Regulates Functional Maturation of Murine Beta Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Jun 10

PMID 28598424

Citations 43

Authors

Qicheng Ni

Yanyun Gu

Yun Xie

Qinglei Yin

Hongli Zhang

Aifang Nie

Wenyi Li

Yanqiu Wang

Guang Ning

Weiqing Wang

Qidi Wang

Affiliations

Soon will be listed here.

Abstract

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.

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