ArticlePloS one2011
ENPP1 affects insulin action and secretion: evidences from in vitro studies.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Genome-wide meta-analysis of genetic susceptible genes for Type 2 Diabetes.BMC systems biology · 2012Pooled it
- Replication Study of ENPP1 Variants and Haplotypes Associated with Severe Obesity in a Greek Adult Population.Biochemical genetics · 2026Article
- A Novel PPARG R212W Variant Causes Familial Partial Lipodystrophy Type 3: Clinical Presentation and Functional Characterization.International journal of molecular sciences · 2026Article
- Transcriptomic and epigenomic signatures of liver metabolism and insulin sensitivity in aging mice.Mechanisms of ageing and development · 2025Article
- Endogenous cell membrane interactome mapping for the GLP-1 receptor in different cell types.Nature chemical biology · 2025Article
- Free amino acids accelerate the time-dependent inactivation of rat liver nucleotide pyrophosphatase/phosphodiesterase Enpp3 elicited by EDTA.Amino acids · 2024Article
- GALNT2 expression is associated with glucose control and serum metabolites in patients with type 2 diabetes.Acta diabetologica · 2024Article
- Mechanistic insights of soluble uric acid-induced insulin resistance: Insulin signaling and beyond.Reviews in endocrine & metabolic disorders · 2023Review
- Human antibodies targeting ENPP1 as candidate therapeutics for cancers.Frontiers in immunology · 2023Article
- From Myricetin to the Discovery of Novel Natural Human ENPP1 Inhibitors: A Virtual Screening, Molecular Docking, Molecular Dynamics Simulation, and MM/GBSA Study.Molecules (Basel, Switzerland) · 2022Article
- Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis.International journal of molecular sciences · 2022Review
- Scientific Advances in Diabetes: The Impact of the Innovative Medicines Initiative.Frontiers in medicine · 2021Review
- GALNT2 as a novel modulator of adipogenesis and adipocyte insulin signaling.International journal of obesity (2005) · 2019Article
- Review
- Insulin receptor signaling and glucagon-like peptide 1 effects on pancreatic beta cells.PloS one · 2017Article
- FKBP51 inhibits GSK3β and augments the effects of distinct psychotropic medications.Molecular psychiatry · 2016Article
- Loss of microRNA-27b contributes to breast cancer stem cell generation by activating ENPP1.Nature communications · 2015Article
- Dual Opposing Roles of Metallothionein Overexpression in C57BL/6J Mouse Pancreatic β-Cells.PloS one · 2015Article
- Aberrant liver insulin receptor isoform a expression normalises with remission of type 2 diabetes after gastric bypass surgery.PloS one · 2015Article
- Proteomic Analysis of Disease Stratified Human Pancreas Tissue Indicates Unique Signature of Type 1 Diabetes.PloS one · 2015Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The aim of this study was to deeper investigate the mechanisms through which ENPP1, a negative modulator of insulin receptor (IR) activation, plays a role on insulin signaling, insulin secretion and eventually glucose metabolism. ENPP1 cDNA (carrying either K121 or Q121 variant) was transfected in HepG2 liver-, L6 skeletal muscle- and INS1E beta-cells. Insulin-induced IR-autophosphorylation (HepG2, L6, INS1E), Akt-Ser(473), ERK1/2-Thr(202)/Tyr(204) and GSK3-beta Ser(9) phosphorylation (HepG2, L6), PEPCK mRNA levels (HepG2) and 2-deoxy-D-glucose uptake (L6) was studied. GLUT 4 mRNA (L6), insulin secretion and caspase-3 activation (INS1E) were also investigated. Insulin-induced IR-autophosphorylation was decreased in HepG2-K, L6-K, INS1E-K (20%, 52% and 11% reduction vs. untransfected cells) and twice as much in HepG2-Q, L6-Q, INS1E-Q (44%, 92% and 30%). Similar data were obtained with Akt-Ser(473), ERK1/2-Thr(202)/Tyr(204) and GSK3-beta Ser(9) in HepG2 and L6. Insulin-induced reduction of PEPCK mRNA was progressively lower in untransfected, HepG2-K and HepG2-Q cells (65%, 54%, 23%). Insulin-induced glucose uptake in untransfected L6 (60% increase over basal), was totally abolished in L6-K and L6-Q cells. GLUT 4 mRNA was slightly reduced in L6-K and twice as much in L6-Q (13% and 25% reduction vs. untransfected cells). Glucose-induced insulin secretion was 60% reduced in INS1E-K and almost abolished in INS1E-Q. Serum deficiency activated caspase-3 by two, three and four folds in untransfected INS1E, INS1E-K and INS1E-Q. Glyburide-induced insulin secretion was reduced by 50% in isolated human islets from homozygous QQ donors as compared to those from KK and KQ individuals. Our data clearly indicate that ENPP1, especially when the Q121 variant is operating, affects insulin signaling and glucose metabolism in skeletal muscle- and liver-cells and both function and survival of insulin secreting beta-cells, thus representing a strong pathogenic factor predisposing to insulin resistance, defective insulin secretion and glucose metabolism abnormalities.
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Registered trials
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