ArticleDiabetologia2019
Vascular endothelial PDPK1 plays a pivotal role in the maintenance of pancreatic beta cell mass and function in adult male mice.
Article in Diabetologia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- Article
- The paracrine signalling between endothelial and pancreatic β-cells: implications for oxidative stress and diabetes.Journal of endocrinological investigation · 2026Review
- Obesity-driven microbial GABA depletion promotes metabolic rewiring and colorectal cancer progression.Nature communications · 2026Article
- Endothelial IRE1α promotes thrombospondin-1 mRNA decay and supports metabolic stress adaptation of pancreatic islets.Nature communications · 2026Article
- Molecular mechanism for pancreatic β-cell dysfunction and atherosclerosis.Diabetology international · 2026Review
- Molecular mechanism for pancreatic β-cell dysfunction and atherosclerosis and its therapeutic application: Importance of translational research bridging clinical practice and basic research.Journal of diabetes investigation · 2025Review
- Rescuing vascular dysfunction in dorsal pancreatic arteries prevents tacrolimus-induced glucose metabolism disorder in mice.Molecular medicine (Cambridge, Mass.) · 2025Article
- Review
- 3-Phosphoinositide-Dependent Kinase 1 as a Therapeutic Target for Treating Diabetes.Current diabetes reviews · 2025Review
- Genome-wide screening of m6A profiling of cutaneous wound healing in diabetic mice.Molecular biology reports · 2024Article
- Triple targeting of RSK, AKT, and S6K as pivotal downstream effectors of PDPK1 by TAS0612 in B-cell lymphomas.Cancer science · 2023Article
- Comprehensive Search for GPCR Compounds which Can Enhance MafA and/or PDX-1 Expression Levels Using a Small Molecule Compound Library.Journal of diabetes research · 2023Article
- Imeglimin exerts favorable effects on pancreatic β-cells by improving morphology in mitochondria and increasing the number of insulin granules.Scientific reports · 2022Article
- Article
- Early combination therapy of empagliflozin and linagliptin exerts beneficial effects on pancreatic β cells in diabetic db/db mice.Scientific reports · 2021Article
- Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class.International journal of molecular sciences · 2021Review
- Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History.International journal of molecular sciences · 2021Review
- Neutrophil-Associated Inflammatory Changes in the Pre-Diabetic Pancreas of Early-Age NOD Mice.Frontiers in endocrinology · 2021Article
- Notable Underlying Mechanism for Pancreatic β-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling.International journal of molecular sciences · 2020Review
- VEGF-A and blood vessels: a beta cell perspective.Diabetologia · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe aim of this study was to elucidate the impact of 3'-phosphoinositide-dependent protein kinase-1 (PDPK1) in vascular endothelial cells on the maintenance of pancreatic beta cell mass and function.
methodsMale vascular endothelial cell-specific Pdpk1-knockout mice (Tie2
resultsDuring the IPGTT, the blood glucose level was comparable between knockout mice and control flox mice, although serum insulin level was significantly lower in knockout mice. During the OGTT, glucose tolerance deteriorated slightly in knockout mice, accompanied by a decreased serum insulin level. During an IPGTT after pre-treatment with exendin-4 (Ex-4), glucose tolerance was significantly impaired in knockout mice. In fact, glucose-stimulated insulin secretion of isolated islets from knockout mice was significantly reduced compared with control flox mice, and addition of Ex-4 revealed impaired sensitivity to incretin hormones in islets of knockout mice. In immunohistochemical analyses, both alpha and beta cell masses were significantly reduced in knockout mice. In addition, the CD31-positive area was significantly decreased in islets of knockout mice. The proportion of pimonidazole-positive islets was significantly increased in knockout mice. mRNA expression levels related to insulin biosynthesis (Ins1, Ins2, Mafa, Pdx1 and Neurod [also known as Neurod1]) and beta cell function (such as Gck and Slc2a2) were significantly decreased in islets of knockout mice. Microsphere experiments revealed remarkably reduced islet blood flow. In addition, mRNA expression levels of Hif1α (also known as Hif1a) and its downstream factors such as Adm, Eno1, Tpi1 (also known as Ets1), Hmox1 and Vegfa, were significantly increased in islets of knockout mice, indicating that islets of knockout mice were in a more hypoxic state than those of control flox mice. As a result, mRNA expression levels related to adaptive unfolded protein response and endoplasmic reticulum stress-related apoptotic genes were significantly elevated in islets of knockout mice. In addition, inflammatory cytokine levels were increased in islets of knockout mice. Electron microscopy revealed reduced endothelial fenestration and thickening of basal membrane of vascular endothelium in islets of knockout mice. CONCLUSIONS/
interpretationVascular endothelial PDPK1 plays an important role in the maintenance of pancreatic beta cell mass and function by maintaining vascularity of pancreas and islets and protecting them from hypoxia, hypoxia-related endoplasmic reticulum stress, inflammation and distortion of capillary structure.
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