ArticleThe Journal of clinical investigation2019
mTORC1 to AMPK switching underlies β-cell metabolic plasticity during maturation and diabetes.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
92 citing papers in PubMed, 122 citations in OpenAlex.
- Postnatal refinement of CaChannels (Austin, Tex.) · 2026Article
- Nutrient and non-nutrient regulators of insulin secretion.Nature reviews. Endocrinology · 2026Review
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Metabolic Programming of β-Cell Fate, State, and Function through Time and Space.Physiology (Bethesda, Md.) · 2026Review
- Hypoglycemic conditions enhance neonatal β-cell glucose responsiveness via AMPK/mTOR-increased KATP channel density.Endocrinology · 2026Article
- Presenilin-1 controls glycolysis and identity of pancreatic beta cells.Communications biology · 2026Article
- The myokine irisin ameliorates the secretory dysfunction of pancreatic β cells in experimental and human type 2 diabetes.Science advances · 2026Article
- Impaired glucose tolerance and mild diabetes induce β-cell dysfunction in mice.Nature communications · 2026Article
- Declining FXR expression coordinates neonatal beta cell mass development with microbial bile acid metabolism maturation in mice.Diabetologia · 2026Article
- Paligenosis: dual potential of mature cell plasticity in regeneration and tumorigenesis.MedScience · 2026Review
- Article
- Rheb1 signaling and the fate of pancreatic β cells: Toward a new frontier in diabetes therapy.World journal of diabetes · 2025Article
- The role of AMPK signaling pathway in the pathogenesis of type 2 diabetes mellitus with its complications and related metabolic disorders.Metabolism open · 2025Review
- Placental mTOR signalling links mitochondrial dysfunction, nutrient transport and neonatal beta cell perturbations in mice.Diabetologia · 2025Article
- Integrated proteomic analysis identifies TYMS-dependent AMPK-mTOR signaling in pancreatic neuroendocrine tumors.iScience · 2025Article
- Advancements in photobiomodulation for generating functional beta cells from adipose derived stem cells in 3D culture: a comprehensive review.Stem cell research & therapy · 2025Review
- Rheb1 as a novel β-cell regulator connecting mTORC1, AMPK, and NOTCH1 pathways for efficient diabetes therapy.World journal of diabetes · 2025Article
- Vitamin D receptor signalling regulates the diet-driven metabolic shift during weaning.Molecular metabolism · 2025Article
- FXYD2 marks and regulates maturity of β cells via ion channel-mediated signal transduction.Nature communications · 2025Article
- β-Cell Dedifferentiation in HOMA-βlow and HOMA-βhigh Subjects.The Journal of clinical endocrinology and metabolism · 2025Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Pancreatic beta cells (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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.