ArticleDiabetologia2014
In vivo activation of the PI3K-Akt pathway in mouse beta cells by the EGFR mutation L858R protects against diabetes.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Elevated MANF expression in β cells protects mice from streptozotocin-induced diabetes by attenuating islet stress and immunogenicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Red blood cell distribution width to albumin ratio is associated with osteoarthritis prevalence among US adults with diabetes using data from NHANES 2005 to 2018.Scientific reports · 2025Article
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
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- Investigation of Pancreatic-beta Cells Role in the Biological Process of Ageing.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Metformin Preserves Insulin Secretion in Pancreatic β-cells through FGF21/Akt PathwayCombinatorial chemistry & high throughput screening · 2024Article
- Urolithin C alleviates pancreatic β-cell dysfunction in type 1 diabetes by activating Nrf2 signaling.Nutrition & diabetes · 2023Article
- The amphiregulin/EGFR axis has limited contribution in controlling autoimmune diabetes.Scientific reports · 2023Article
- Glucolipotoxic Stress-Induced Mig6 Desensitizes EGFR Signaling and Promotes Pancreatic Beta Cell Death.Metabolites · 2023Article
- A single-cell human islet interactome atlas identifies disrupted autocrine and paracrine communications in type 2 diabetes.NAR genomics and bioinformatics · 2022Article
- Targeting the PI3K/Akt signaling pathway in pancreatic β-cells to enhance their survival and function: An emerging therapeutic strategy for type 1 diabetes.Journal of diabetes · 2022Review
- Carnosic Acid Protects INS-1 β-Cells against Streptozotocin-Induced Damage by Inhibiting Apoptosis and Improving Insulin Secretion and Glucose Uptake.Molecules (Basel, Switzerland) · 2022Article
- The parasite-derived peptide FhHDM-1 activates the PI3K/Akt pathway to prevent cytokine-induced apoptosis of β-cells.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Kinome Profiling Reveals Abnormal Activity of Kinases in Skeletal Muscle From Adults With Obesity and Insulin Resistance.The Journal of clinical endocrinology and metabolism · 2020Article
- Generation of insulin-secreting cells from mouse gallbladder stem cells by small molecules in vitro.Stem cell research & therapy · 2019Article
- MicroRNA-351 eases insulin resistance and liver gluconeogenesis via the PI3K/AKT pathway by inhibiting FLOT2 in mice of gestational diabetes mellitus.Journal of cellular and molecular medicine · 2019Article
- Pancreatic fibroblast growth factor 21 protects against type 2 diabetes in mice by promoting insulin expression and secretion in a PI3K/Akt signaling-dependent manner.Journal of cellular and molecular medicine · 2019Article
- EGF suppresses the expression of miR-124a in pancreatic β cell lines via ETS2 activation through the MEK and PI3K signaling pathways.International journal of biological sciences · 2019Article
- Cellular signaling pathways regulating β-cell proliferation as a promising therapeutic target in the treatment of diabetes.Experimental and therapeutic medicine · 2018Review
- Epidermal Growth Factor Receptor Signaling Regulates β Cell Proliferation in Adult Mice.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisEGF receptor (EGFR) signalling is required for normal beta cell development and postnatal beta cell proliferation. We tested whether beta cell proliferation can be triggered by EGFR activation at any age and whether this can protect beta cells against apoptosis induced by diabetogenic insults in a mouse model.
methodsWe generated transgenic mice with doxycycline-inducible expression of constitutively active EGFR (L858R) (CA-EGFR) under the insulin promoter. Mice were given doxycycline at various ages for different time periods, and beta cell proliferation and mass were analysed. Mice were also challenged with streptozotocin and isolated islets exposed to cytokines.
resultsExpression of EGFR (L858R) led to increased phosphorylation of EGFR and Akt in pancreatic islets. CA-EGFR expression during pancreatic development (embryonic day [E]12.5 to postnatal day [P]1) increased beta cell proliferation and mass in newborn mice. However, CA-EGFR expression in adult mice did not affect beta cell mass. Expression of the transgene improved glycaemia and markedly inhibited beta cell apoptosis after a single high dose, as well as after multiple low doses of streptozotocin. In vitro mechanistic studies showed that CA-EGFR protected isolated islets from cytokine-mediated beta cell death, possibly by repressing the proapoptotic protein BCL2-like 11 (BIM). CONCLUSIONS/
interpretationOur findings show that the expression of CA-EGFR in the developing, but not in the adult pancreas stimulates beta cell replication and leads to increased beta cell mass. Importantly, CA-EGFR protects beta cells against streptozotocin- and cytokine-induced death.
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