ArticleDiabetes2020
Mitochondrial Proton Leak Regulated by Cyclophilin D Elevates Insulin Secretion in Islets at Nonstimulatory Glucose Levels.
Article in Diabetes, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 43 citations in OpenAlex.
- The protein deacetylase SIRT2 exerts metabolic control over adaptive β cell proliferation.The Journal of clinical investigation · 2025Article
- Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis.JCI insight · 2025Article
- Single-cell decoding of human islet cell type-specific alterations in type 2 diabetes reveals converging genetic- and state-drivenbioRxiv : the preprint server for biology · 2025Article
- The Proton Leak of the Inner Mitochondrial Membrane Is Enlarged in Freshly Isolated Pancreatic Islets.Biomedicines · 2024Article
- Review
- A role and mechanism for redox sensing by SENP1 in β-cell responses to high fat feeding.Nature communications · 2024Article
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- Mitochondrial morphology controls fatty acid utilization by changing CPT1 sensitivity to malonyl-CoA.The EMBO journal · 2023Article
- Discovery and molecular basis of subtype-selective cyclophilin inhibitors.Nature chemical biology · 2022Article
- Lipotoxicity in a Vicious Cycle of Pancreatic Beta Cell Exhaustion.Biomedicines · 2022Article
- Metabolic cycles and signals for insulin secretion.Cell metabolism · 2022Review
- Mitofusins Mfn1 and Mfn2 Are Required to Preserve Glucose- but Not Incretin-Stimulated β-Cell Connectivity and Insulin Secretion.Diabetes · 2022Article
- Pulsatile Basal Insulin Secretion Is Driven by Glycolytic Oscillations.Physiology (Bethesda, Md.) · 2022Review
- Deletion of ABCB10 in beta-cells protects from high-fat diet induced insulin resistance.Molecular metabolism · 2022Article
- Review
- On the causal relationships between hyperinsulinaemia, insulin resistance, obesity and dysglycaemia in type 2 diabetes.Diabetologia · 2021Article
- Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease.Cell reports · 2021Article
- Aberrant activity of mitochondrial NCLX is linked to impaired synaptic transmission and is associated with mental retardation.Communications biology · 2021Article
- GRK2 contributes to glucose mediated calcium responses and insulin secretion in pancreatic islet cells.Scientific reports · 2021Article
- Perilipin 2 downregulation in β cells impairs insulin secretion under nutritional stress and damages mitochondria.JCI insight · 2021Article
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 4 countries.
Funding
Abstract
Fasting hyperinsulinemia precedes the development of type 2 diabetes. However, it is unclear whether fasting insulin hypersecretion is a primary driver of insulin resistance or a consequence of the progressive increase in fasting glycemia induced by insulin resistance in the prediabetic state. Herein, we have discovered a mechanism that specifically regulates non-glucose-stimulated insulin secretion (NGSIS) in pancreatic islets that is activated by nonesterified free fatty acids, the major fuel used by β-cells during fasting. We show that the mitochondrial permeability transition pore regulator cyclophilin D (CypD) promotes NGSIS, but not glucose-stimulated insulin secretion, by increasing mitochondrial proton leak. Islets from prediabetic obese mice show significantly higher CypD-dependent proton leak and NGSIS compared with lean mice. Proton leak-mediated NGSIS is conserved in human islets and is stimulated by exposure to nonesterified free fatty acids at concentrations observed in obese subjects. Mechanistically, proton leak activates islet NGSIS independently of mitochondrial ATP synthesis but ultimately requires closure of the K
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.