ArticlePhysiological reports2016
Role of prolyl hydroxylase domain proteins in the regulation of insulin secretion.
Article in Physiological reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- <p>Prolyl hydroxylase domain proteins: Localization, regulation, function and their role in erythropoiesis (Review)</p>.Molecular medicine reports · 2026Review
- Evaluating the impact of lipids in isolated islet research.Frontiers in endocrinology · 2025Review
- Interplay of hypoxia, immune dysregulation, and metabolic stress in pathophysiology of type 1 diabetes.Frontiers in immunology · 2025Review
- [Latest Findings on the Role of α-Ketoglutarate in Metabolic Syndrome].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
- Kinetic modelling of β-cell metabolism reveals control points in the insulin-regulating pyruvate cycling pathways.IET systems biology · 2023Article
- Isoform-specific Roles of Prolyl Hydroxylases in the Regulation of Pancreatic β-Cell Function.Endocrinology · 2022Article
- Prolyl-4-hydroxylase 3 maintains β cell glucose metabolism during fatty acid excess in mice.JCI insight · 2021Article
- Hypoxia-inducible factors and diabetes.The Journal of clinical investigation · 2020Review
- The role of α-ketoglutarate and the hypoxia sensing pathway in the regulation of pancreatic β-cell function.Islets · 2020Review
- Eicosapentaenoic Acid (EPA) Modulates Glucose Metabolism by Targeting AMP-Activated Protein Kinase (AMPK) Pathway.International journal of molecular sciences · 2019Article
- Cluster-assembled zirconia substrates promote long-term differentiation and functioning of human islets of Langerhans.Scientific reports · 2018Article
- Piperine regulates UCP1 through the AMPK pathway by generating intracellular lactate production in muscle cells.Scientific reports · 2017Article
- Role of prolyl hydroxylase domain proteins in the regulation of insulin secretion.Physiological reports · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes is associated with impaired nutrient-regulated anaplerosis and insulin secretion in pancreatic β-cells. One key anaplerotic substrate that may be involved in regulating insulin release is α-ketoglutarate (αKG). Since prolyl hydroxylase domain proteins (PHDs) can metabolize cytosolic αKG, we sought to explore the role of this enzyme in the regulation of β-cell function. The oxygen-sensing PHDs regulate the stability of hypoxia-inducible factor 1α (HIF1α) as well as other proline-containing proteins by catalyzing the hydroxylation of proline residues. This reaction is dependent on sufficient levels of oxygen, iron, and αKG. In the present study, we utilized both pharmacological and genetic approaches to assess the impact of inhibiting PHD activity on β-cell function. We demonstrate that ethyl-3,4-dihydroxybenzoate (EDHB), a PHD inhibitor, significantly blunted glucose-stimulated insulin secretion (GSIS) from 832/13 clonal cells, rat, and human islets. EDHB reduced glucose utilization, ATP/ADP ratio, and key TCA cycle intermediates such as pyruvate, citrate, fumarate, and malate. siRNA-mediated knockdown of PHD1 and PHD3 inhibited GSIS, whereas siRNA-mediated knockdown of PHD2 had no effect on GSIS. Taken together, the current results demonstrate an important role for PHDs as mediators of islet insulin secretion.
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