ArticleDiabetes2009
Upregulation of the mammalian target of rapamycin complex 1 pathway by Ras homolog enriched in brain in pancreatic beta-cells leads to increased beta-cell mass and prevention of hyperglycemia.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 92 citations in OpenAlex.
- Article
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- Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System.Biomolecules · 2023Review
- The Metabolic Basis for Nervous System Dysfunction in Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease.Current neurovascular research · 2023Article
- Review
- Pseudotime Ordering Single-Cell Transcriptomic of β Cells Pancreatic Islets in Health and Type 2 Diabetes.Phenomics (Cham, Switzerland) · 2021Article
- Nicotinamide as a Foundation for Treating Neurodegenerative Disease and Metabolic Disorders.Current neurovascular research · 2021Review
- New Insights for nicotinamide: Metabolic disease, autophagy, and mTOR.Frontiers in bioscience (Landmark edition) · 2020Review
- A Nutrient-Sensing Transition at Birth Triggers Glucose-Responsive Insulin Secretion.Cell metabolism · 2020Article
- Dysregulation of metabolic flexibility: The impact of mTOR on autophagy in neurodegenerative disease.International review of neurobiology · 2020Review
- Nicotinamide: Oversight of Metabolic Dysfunction Through SIRT1, mTOR, and Clock Genes.Current neurovascular research · 2020Review
- Cognitive impairment with diabetes mellitus and metabolic disease: innovative insights with the mechanistic target of rapamycin and circadian clock gene pathways.Expert review of clinical pharmacology · 2020Review
- Nutrient Sensor mTOR and OGT: Orchestrators of Organelle Homeostasis in PancreaticJournal of diabetes research · 2020Review
- mTORC1 Overactivation as a Key Aging Factor in the Progression to Type 2 Diabetes Mellitus.Frontiers in endocrinology · 2018Review
- Overexpression of Kinase-Dead mTOR Impairs Glucose Homeostasis by Regulating Insulin Secretion and Not β-Cell Mass.Diabetes · 2017Article
- Effects of mTOR inhibition on cardiac and adipose tissue pathology and glucose metabolism in rats with metabolic syndrome.Pharmacology research & perspectives · 2017Article
- The Molecular Mechanism of Glucagon-Like Peptide-1 Therapy in Alzheimer's Disease, Based on a Mechanistic Target of Rapamycin Pathway.CNS drugs · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveComponents of insulin/IGF-1 receptor-mediated signaling pathways in pancreatic beta-cells have been implicated in the development of diabetes, in part through the regulation of beta-cell mass in vivo. Studies in vitro have shown that the protein Ras homolog enriched in brain (Rheb) plays a key role as a positive upstream regulator of the mammalian target of rapamycin complex 1 (mTORC1) pathway in integrating inputs from nutrients and growth factors for cell growth. Our objective was to investigate the role of the mTORC1 pathway in the regulation of beta-cell mass in vivo. RESEARCH DESIGN AND
methodsWe generated transgenic mice that overexpress Rheb in beta-cells. We examined the activation of the mTORC1 pathway and its effects on beta-cell mass, on glucose metabolism, and on protection against hyperglycemia.
resultsImmunoblots of islet extracts revealed that the phosphorylation levels of ribosomal protein S6 and eukaryotic initiation factor 4E binding protein 1, downstream effectors for mTORC1, were upregulated in transgenic beta-cells. Immunostaining of the pancreatic sections with anti-phospho-S6 antibody confirmed upregulation of the mTORC1 pathway in beta-cells in vivo. The mice showed improved glucose tolerance with higher insulin secretion. This arose from increased beta-cell mass accompanied by increased cell size. The mice also exhibited resistance to hyperglycemia induced by streptozotocin and obesity.
conclusionsActivation of the mTORC1 pathway by Rheb led to increased beta-cell mass in this mouse model without producing obvious unfavorable effects, giving a potential approach for the treatment of beta-cell failure and diabetes.
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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 Socratic graph.