ArticleThe Journal of clinical investigation2017
Loss of mTORC1 signaling alters pancreatic α cell mass and impairs glucagon secretion.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Targeting cellular senescence with Traditional Chinese Medicine: advances in neurodegenerative disorder treatment.Frontiers in neurology · 2026Pooled it
- CBP/p300 is critical for the expansion and maintenance of functional pancreatic α cell mass.Nature communications · 2026Article
- SEL1L-HRD1 ER-associated degradation facilitates prohormone convertase 2 maturation and glucagon production in islet α cells.Nature communications · 2026Article
- Blockade of glucagon receptor induces α-cell hypersecretion by hyperaminoacidemia in mice.Nature communications · 2025Article
- Fasting Mimicking Diet for Metabolic Syndrome: A Narrative Review of Human Studies.Metabolites · 2025Review
- Hyperglucagonemia and glucagon hypersecretion in early type 2 diabetes result from multifaceted dysregulation of pancreatic mouse α-cells.Pflugers Archiv : European journal of physiology · 2025Article
- Liver-specific glucagon dysfunction promotes PP-cell hyperplasia and formation of glucagon and PP double-positive cells.PloS one · 2025Article
- Diagnostic characteristics, treatment outcomes, and prognostic factors in glucagonomas.Endocrine oncology (Bristol, England) · 2025Article
- Autophagy-lysosome pathway in insulin & glucagon homeostasis.Frontiers in endocrinology · 2025Review
- CK2 activity is crucial for proper glucagon expression.Diabetologia · 2024Article
- Hyperglucagonaemia in diabetes: altered amino acid metabolism triggers mTORC1 activation, which drives glucagon production.Diabetologia · 2023Article
- The Regulation and Secretion of Glucagon in Response to Nutrient Composition: Unraveling Their Intricate Mechanisms.Nutrients · 2023Review
- Metabolic regulation of glucagon secretion.The Journal of endocrinology · 2023Article
- Time-dependent effects of endogenous hyperglucagonemia on glucose homeostasis and hepatic glucagon action.JCI insight · 2023Article
- Long-term administration of sirolimus does not affect the physical development of children with tuberous sclerosis complex.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022Article
- Acetyl-CoA-carboxylase 1 (ACC1) plays a critical role in glucagon secretion.Communications biology · 2022Article
- Lesch-Nyhan disease causes impaired energy metabolism and reduced developmental potential in midbrain dopaminergic cells.Stem cell reports · 2021Article
- Rapamycin administration during an acute heat stress challenge in growing pigs.Journal of animal science · 2021Article
- The Role of Oxidative Stress in Pancreatic β Cell Dysfunction in Diabetes.International journal of molecular sciences · 2021Review
- Glucagon Resistance and Decreased Susceptibility to Diabetes in a Model of Chronic Hyperglucagonemia.Diabetes · 2021Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
Abstract
Glucagon plays a major role in the regulation of glucose homeostasis during fed and fasting states. However, the mechanisms responsible for the regulation of pancreatic α cell mass and function are not completely understood. In the current study, we identified mTOR complex 1 (mTORC1) as a major regulator of α cell mass and glucagon secretion. Using mice with tissue-specific deletion of the mTORC1 regulator Raptor in α cells (αRaptorKO), we showed that mTORC1 signaling is dispensable for α cell development, but essential for α cell maturation during the transition from a milk-based diet to a chow-based diet after weaning. Moreover, inhibition of mTORC1 signaling in αRaptorKO mice and in WT animals exposed to chronic rapamycin administration decreased glucagon content and glucagon secretion. In αRaptorKO mice, impaired glucagon secretion occurred in response to different secretagogues and was mediated by alterations in KATP channel subunit expression and activity. Additionally, our data identify the mTORC1/FoxA2 axis as a link between mTORC1 and transcriptional regulation of key genes responsible for α cell function. Thus, our results reveal a potential function of mTORC1 in nutrient-dependent regulation of glucagon secretion and identify a role for mTORC1 in controlling α cell-mass maintenance.
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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.