Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact

Usage Information

mTORC1-to-AMPK switching underlies β cell metabolic plasticity during maturation and diabetes
Rami Jaafar, … , Suneil K. Koliwad, Anil Bhushan
Rami Jaafar, … , Suneil K. Koliwad, Anil Bhushan
Published July 2, 2019
Citation Information: J Clin Invest. 2019;129(10):4124-4137. https://doi.org/10.1172/JCI127021.
View: Text | PDF
Research Article Endocrinology

mTORC1-to-AMPK switching underlies β cell metabolic plasticity during maturation and diabetes

  • Text
  • PDF
Abstract

Pancreatic β cells differentiate during fetal life, but only postnatally acquire the capacity for glucose-stimulated insulin secretion (GSIS). How this happens is not clear. In exploring what molecular mechanisms drive the maturation of β cell function, we found that the control of cellular signaling in β cells fundamentally switched from the nutrient sensor target of rapamycin (mTORC1) to the energy sensor 5′-adenosine monophosphate–activated protein kinase (AMPK), and that this was critical for functional maturation. Moreover, AMPK was activated by the dietary transition taking place during weaning, and this in turn inhibited mTORC1 activity to drive the adult β cell phenotype. While forcing constitutive mTORC1 signaling in adult β cells relegated them to a functionally immature phenotype with characteristic transcriptional and metabolic profiles, engineering the switch from mTORC1 to AMPK signaling was sufficient to promote β cell mitochondrial biogenesis, a shift to oxidative metabolism, and functional maturation. We also found that type 2 diabetes, a condition marked by both mitochondrial degeneration and dysregulated GSIS, was associated with a remarkable reversion of the normal AMPK-dependent adult β cell signature to a more neonatal one characterized by mTORC1 activation. Manipulating the way in which cellular nutrient signaling pathways regulate β cell metabolism may thus offer new targets to improve β cell function in diabetes.

Authors

Rami Jaafar, Stella Tran, Ajit N. Shah, Gao Sun, Martin Valdearcos, Piero Marchetti, Matilde Masini, Avital Swisa, Simone Giacometti, Ernesto Bernal-Mizrachi, Aleksey Matveyenko, Matthias Hebrok, Yuval Dor, Guy A. Rutter, Suneil K. Koliwad, Anil Bhushan

×

Usage data is cumulative from January 2020 through January 2021.

Usage JCI PMC
Text version 2,372 499
PDF 433 511
Figure 774 0
Supplemental data 161 31
Citation downloads 36 0
Totals 3,776 1,041
Total Views 4,817

Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.

Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.

Advertisement
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts