ArticleDiabetologia2016
Inactivation of class II PI3K-C2α induces leptin resistance, age-dependent insulin resistance and obesity in male mice.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- A meta-analysis of genome-wide association studies for average daily gain and lean meat percentage in two Duroc pig populations.BMC genomics · 2021Pooled it
- Transcriptome analysis unveils multiple reasons behind delayed and slower deposition of intramuscular fat compared to subcutaneous fat in cattle.BMC genomics · 2025Article
- Inactivation of PI3K-C2α deregulates cell death pathways and sensitizes to endotoxic shock.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting PI3K family with small-molecule inhibitors in cancer therapy: current clinical status and future directions.Molecular cancer · 2024Review
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- Targeting Class I-II-III PI3Ks in Cancer Therapy: Recent Advances in Tumor Biology and Preclinical Research.Cancers · 2023Review
- Structural basis of phosphatidylinositol 3-kinase C2α function.Nature structural & molecular biology · 2022Article
- An Overview of Class II Phosphoinositide 3-Kinases.Current topics in microbiology and immunology · 2022Article
- Potential Prognostic Biomarkers of NIMA (Never in Mitosis, Gene A)-Related Kinase (NEK) Family Members in Breast Cancer.Journal of personalized medicine · 2021Article
- Class II phosphatidylinositol 3-kinase isoforms in vesicular trafficking.Biochemical Society transactions · 2021Review
- Exploring the genetic architecture of feed efficiency traits in chickens.Scientific reports · 2021Article
- Efficacy of Providing the PI3K p110α Inhibitor BYL719 (Alpelisib) to Middle-Aged Mice in Their Diet.Biomolecules · 2021Article
- Phosphatidylinositol 3-monophosphate: A novel actor in thrombopoiesis and thrombosis.Research and practice in thrombosis and haemostasis · 2020Review
- PI3K inhibitors in thrombosis and cardiovascular disease.Clinical and translational medicine · 2020Review
- PI3K isoforms in cell signalling and vesicle trafficking.Nature reviews. Molecular cell biology · 2019Review
- Revisiting PI3-kinase signalling in angiogenesis.Vascular biology (Bristol, England) · 2019Review
- Vps34 PI 3-kinase inactivation enhances insulin sensitivity through reprogramming of mitochondrial metabolism.Nature communications · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
aims/hypothesisWhile the class I phosphoinositide 3-kinases (PI3Ks) are well-documented positive regulators of metabolism, the involvement of class II PI3K isoforms (PI3K-C2α, -C2β and -C2γ) in metabolic regulation is just emerging. Organismal inactivation of PI3K-C2β increases insulin signalling and sensitivity, whereas PI3K-C2γ inactivation has a negative metabolic impact. In contrast, the role of PI3K-C2α in organismal metabolism remains unexplored. In this study, we investigated whether kinase inactivation of PI3K-C2α affects glucose metabolism in mice.
methodsWe have generated and characterised a mouse line with a constitutive inactivating knock-in (KI) mutation in the kinase domain of the gene encoding PI3K-C2α (Pik3c2a).
resultsWhile homozygosity for kinase-dead PI3K-C2α was embryonic lethal, heterozygous PI3K-C2α KI mice were viable and fertile, with no significant histopathological findings. However, male heterozygous mice showed early onset leptin resistance, with a defect in leptin signalling in the hypothalamus, correlating with a mild, age-dependent obesity, insulin resistance and glucose intolerance. Insulin signalling was unaffected in insulin target tissues of PI3K-C2α KI mice, in contrast to previous reports in which downregulation of PI3K-C2α in cell lines was shown to dampen insulin signalling. Interestingly, no metabolic phenotypes were detected in female PI3K-C2α KI mice at any age. CONCLUSIONS/
interpretationOur data uncover a sex-dependent role for PI3K-C2α in the modulation of hypothalamic leptin action and systemic glucose homeostasis. ACCESS TO RESEARCH MATERIALS: All reagents are available upon request.
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