ArticleDiabetologia2013
Imatinib mesilate-induced phosphatidylinositol 3-kinase signalling and improved survival in insulin-producing cells: role of Src homology 2-containing inositol 5'-phosphatase interaction with c-Abl.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Impact of Imatinib Therapy on Immunometabolism to Promote β-Cell Survival in Diabetes.Journal of diabetes · 2026Article
- Nilotinib-induced Diabetes in Japanese Patients with Chronic Myeloid Leukemia.Internal medicine (Tokyo, Japan) · 2025Article
- GDF15 Protects Insulin-Producing Beta Cells against Pro-Inflammatory Cytokines and Metabolic Stress via Increased Deamination of Intracellular Adenosine.International journal of molecular sciences · 2024Article
- Abl kinases can function as suppressors of tumor progression and metastasis.Frontiers in oncology · 2023Article
- Are off-target effects of imatinib the key to improving beta-cell function in diabetes?Upsala journal of medical sciences · 2022Review
- Short-Term Protocols to Obtain Insulin-Producing Cells from Rat Adipose Tissue: Signaling Pathways and In Vivo Effect.International journal of molecular sciences · 2019Article
- Glucocorticoids and checkpoint tyrosine kinase inhibitors stimulate rat pancreatic beta cell proliferation differentially.PloS one · 2019Article
- Effect of imatinib on plasma glucose concentration in subjects with chronic myeloid leukemia and gastrointestinal stromal tumor.BMC endocrine disorders · 2018Article
- Immune Mechanisms and Pathways Targeted in Type 1 Diabetes.Current diabetes reports · 2018Review
- Nutrient regulation of β-cell function: what do islet cell/animal studies tell us?European journal of clinical nutrition · 2017Review
- c-Abl inhibition mitigates diet-induced obesity through improving insulin sensitivity of subcutaneous fat in mice.Diabetologia · 2017Article
- The green tea polyphenol EGCG potentiates the antiproliferative activity of sunitinib in human cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Imatinib and Nilotinib increase glioblastoma cell invasion via Abl-independent stimulation of p130Cas and FAK signalling.Scientific reports · 2016Article
- Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome.Upsala journal of medical sciences · 2016Article
- Angiotensin II down-regulates nephrin-Akt signaling and induces podocyte injury: roleof c-Abl.Molecular biology of the cell · 2016Article
- Article
- PI3K is involved in β1 integrin clustering by PSGL-1 and promotes β1 integrin-mediated Jurkat cell adhesion to fibronectin.Molecular and cellular biochemistry · 2014Article
- Tyrosine Kinase Targeting: A Potential Therapeutic Strategy for Diabetes.Saudi journal of medicine & medical sciencesReview
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisIt is not clear how small tyrosine kinase inhibitors, such as imatinib mesilate, protect against diabetes and beta cell death. The aim of this study was to determine whether imatinib, as compared with the non-cAbl-inhibitor sunitinib, affects pro-survival signalling events in the phosphatidylinositol 3-kinase (PI3K) pathway.
methodsHuman EndoC-βH1 cells, murine beta TC-6 cells and human pancreatic islets were used for immunoblot analysis of insulin receptor substrate (IRS)-1, Akt and extracellular signal-regulated kinase (ERK) phosphorylation. Phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] plasma membrane concentrations were assessed in EndoC-βH1 and MIN6 cells using evanescent wave microscopy. Src homology 2-containing inositol 5'-phosphatase 2 (SHIP2) tyrosine phosphorylation and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) serine phosphorylation, as well as c-Abl co-localisation with SHIP2, were studied in HEK293 and EndoC-βH1 cells by immunoprecipitation and immunoblot analysis. Gene expression was assessed using RT-PCR. Cell viability was measured using vital staining.
resultsImatinib stimulated ERK(thr202/tyr204) phosphorylation in a c-Abl-dependent manner. Imatinib, but not sunitinib, also stimulated IRS-1(tyr612), Akt(ser473) and Akt(thr308) phosphorylation. This effect was paralleled by oscillatory bursts in plasma membrane PI(3,4,5)P3 levels. Wortmannin induced a decrease in PI(3,4,5)P3 levels, which was slower in imatinib-treated cells than in control cells, indicating an effect on PI(3,4,5)P3-degrading enzymes. In line with this, imatinib decreased the phosphorylation of SHIP2 but not of PTEN. c-Abl co-immunoprecipitated with SHIP2 and its binding to SHIP2 was largely reduced by imatinib but not by sunitinib. Imatinib increased total β-catenin levels and cell viability, whereas sunitinib exerted negative effects on cell viability. CONCLUSIONS/
interpretationImatinib inhibition of c-Abl in beta cells decreases SHIP2 activity, which results in enhanced signalling downstream of PI3 kinase.
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