ArticleAmerican journal of physiology. Endocrinology and metabolism2010
ß-Cell-specific pyruvate dehydrogenase deficiency impairs glucose-stimulated insulin secretion.
Article in American journal of physiology. Endocrinology and metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Branched-chain α-keto acids impair glucose-stimulated insulin secretion in pancreatic β-cells under diabetes by reactivating the LDHA-lactate axis.Nature communications · 2026Article
- Animal models of pyruvate dehydrogenase complex deficiency: insight into mechanisms of cerebral abnormalities and tissue-specific role in metabolism.Frontiers in medicine · 2026Review
- β-Cell Mitochondrial Dysfunction: Underlying Mechanisms and Potential Therapeutic Strategies.Cells · 2025Review
- The mitochondrial enzyme pyruvate carboxylase restricts pancreatic β-cell senescence by blocking p53 activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Identifying patterns differing between high-dimensional datasets with generalized contrastive PCA.bioRxiv : the preprint server for biology · 2024Article
- Simultaneous Measurement of Changes in Mitochondrial and Endoplasmic Reticulum Free Calcium in Pancreatic Beta Cells.Biosensors · 2023Article
- Kinetic and data-driven modeling of pancreatic β-cell central carbon metabolism and insulin secretion.PLoS computational biology · 2022Article
- Biomarkers of autoimmunity and beta cell metabolism in type 1 diabetes.Frontiers in immunology · 2022Review
- Reprogramming of aerobic glycolysis in non-transformed mouse liver with pyruvate dehydrogenase complex deficiency.Physiological reports · 2021Article
- Metabolic Effects of Selective Deletion of Group VIA Phospholipase ABiomolecules · 2020Article
- Conditional knockout of pyruvate dehydrogenase in mouse pancreatic β‑cells causes morphological and functional changes.Molecular medicine reports · 2020Article
- Defining the contribution of skeletal muscle pyruvate dehydrogenase α1 to exercise performance and insulin action.American journal of physiology. Endocrinology and metabolism · 2018Article
- Arsenic exposure induces glucose intolerance and alters global energy metabolism.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Elevated miR-130a/miR130b/miR-152 expression reduces intracellular ATP levels in the pancreatic beta cell.Scientific reports · 2017Article
- An ancestral role for the mitochondrial pyruvate carrier in glucose-stimulated insulin secretion.Molecular metabolism · 2016Article
- Lack of mitochondria-generated acetyl-CoA by pyruvate dehydrogenase complex downregulates gene expression in the hepatic de novo lipogenic pathway.American journal of physiology. Endocrinology and metabolism · 2016Article
- Mitochondrial pyruvate transport: a historical perspective and future research directions.The Biochemical journal · 2015Review
- Exercise increases insulin content and basal secretion in pancreatic islets in type 1 diabetic mice.Experimental diabetes research · 2011Article
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Glucose-stimulated insulin secretion (GSIS) by β-cells requires the generation of ATP from oxidation of pyruvate as well as generation of coupling factors involving three different pyruvate cycling shuttles. The roles of several key enzymes involved in pyruvate cycling in β-cells have been documented using isolated islets and β-cell clonal lines. To investigate the role of the pyruvate dehydrogenase (PDH) complex (PDC) in GSIS, a murine model of β-cell-specific PDH deficiency (β-PDHKO) was created. Pancreatic insulin content was decreased in 1-day-old β-PDHKO male pups and adult male mice. The plasma insulin levels were decreased and blood glucose levels increased in β-PDHKO male mice from neonatal life onward. GSIS was reduced in isolated islets from β-PDHKO male mice with about 50% reduction in PDC activity. Impairment in a glucose tolerance test and in vivo insulin secretion during hyperglycemic clamp was evident in β-PDHKO adults. No change in the number or size of islets was found in pancreata from 4-wk-old β-PDHKO male mice. However, an increase in the mean size of individual β-cells in islets of these mice was observed. These findings show a key role of PDC in GSIS by pyruvate oxidation. This β-PDHKO mouse model represents the first mouse model in which a mitochondrial oxidative enzyme deletion by gene knockout has been employed to demonstrate an altered GSIS by β-cells.
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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.