ArticleDiabetologia2008
The role of pyruvate carboxylase in insulin secretion and proliferation in rat pancreatic beta cells.
Article in Diabetologia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Cross-Study Meta-Analysis of Blood Transcriptomes in Type 2 Diabetes.International journal of molecular sciences · 2025Pooled it
- 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
- 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
- Synthesis and Evaluation of 1,3-Disubstituted Imidazolidine-2,4,5-triones as Inhibitors of Pyruvate Carboxylase.ACS medicinal chemistry letters · 2024Article
- Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease.Cell metabolism · 2024Article
- Insulin therapy in acute decompensation of holocarboxylase synthetase deficiency with hyperglycemia and ketoacidosis.Molecular genetics and metabolism reports · 2024Article
- Kinetic modelling of β-cell metabolism reveals control points in the insulin-regulating pyruvate cycling pathways.IET systems biology · 2023Article
- Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome.Biomolecules · 2023Article
- A pathway model of glucose-stimulated insulin secretion in the pancreaticFrontiers in endocrinology · 2023Article
- An extensive bioinformatics study on the role of mitochondrial solute carrier family 25 in PC and its mechanism behind affecting immune infiltration and tumor energy metabolism.Journal of translational medicine · 2022Article
- Multiple roles played by the mitochondrial citrate carrier in cellular metabolism and physiology.Cellular and molecular life sciences : CMLS · 2022Review
- Luseogliflozin preserves the pancreatic beta-cell mass and function in db/db mice by improving mitochondrial function.Scientific reports · 2022Article
- Article
- Pyruvate as a Potential Beneficial Anion in Resuscitation Fluids.Frontiers in medicine · 2022Article
- Biomarkers of autoimmunity and beta cell metabolism in type 1 diabetes.Frontiers in immunology · 2022Review
- Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets.Cell reports · 2021Article
- Review
- Targeting Pyruvate Carboxylase by a Small Molecule Suppresses Breast Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Conditional knockout of pyruvate dehydrogenase in mouse pancreatic β‑cells causes morphological and functional changes.Molecular medicine reports · 2020Article
- The pivotal role of protein acetylation in linking glucose and fatty acid metabolism to β-cell function.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisPyruvate carboxylase (PC) or pyruvate dehydrogenase (PDH) is required to transfer carbons from pyruvate into the Krebs cycle. PC activity is preserved in the islets of obese animals, but it is reduced in the islets of animal models of type 2 diabetes, suggesting that PC is important in beta cell adaptation to insulin resistance and that PC reduction may lead to beta cell failure.
methodsTo confirm the significance of PC, we first lowered activity using Pc (now known as Pcx) small interfering RNA (siRNA) in INS-1 cells and in dispersed rat islet cells. Second, we overexpressed PC in INS-1 cells, and third, we inhibited PDH by overexpressing the gene encoding pyruvate dehydrogenase kinase 4 (Pdk4) in INS-1 cells.
resultsTreatment of INS-1 cells or dispersed rat islet cells with Pc siRNA resulted in a significant reduction in insulin secretion in both cell types and reduced proliferation in INS-1 cells. This treatment also reduced the content of oxaloacetate, malate and ATP, as well as the NADPH:NADP(+) ratio and activity of the pyruvate-malate shuttle. Overexpression of PC in INS-1 cells led to an elevation of insulin secretion and cell proliferation, whereas inhibition of PDH activity by overexpressing Pdk4 in INS-1 cells did not reduce insulin secretion. CONCLUSIONS/
interpretationOur findings indicate that the PC pathway in beta cells might play a key role in pyruvate metabolism, insulin secretion and cell proliferation.
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