ArticleThe Journal of biological chemistry2013
Actin dynamics regulated by the balance of neuronal Wiskott-Aldrich syndrome protein (N-WASP) and cofilin activities determines the biphasic response of glucose-induced insulin secretion.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
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- Cellular mechanisms of hormone secretion in neuroendocrine tumors: what goes wrong?Frontiers in cell and developmental biology · 2025Review
- CDC42 Regulatory Patterns Related To Inflammatory Bowel Disease and Hyperglycemia.Journal of bioinformatics and systems biology : Open access · 2025Article
- Actin dynamics switches two distinct modes of endosomal fusion in yolk sac visceral endoderm cells.eLife · 2024Article
- In situ structure of actin remodeling during glucose-stimulated insulin secretion using cryo-electron tomography.Nature communications · 2024Article
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
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- α-catenin isoforms are regulated by glucose and involved in regulating insulin secretion in rat clonal β-cell models.The Biochemical journal · 2020Article
- Glucose-dependent phosphorylation signaling pathways and crosstalk to mitochondrial respiration in insulin secreting cells.Cell communication and signaling : CCS · 2019Article
- Cdc42: A Novel Regulator of Insulin Secretion and Diabetes-Associated Diseases.International journal of molecular sciences · 2019Review
- miR-142-3p suppresses uveal melanoma by targeting CDC25C, TGFβR1, GNAQ, WASL, and RAC1.Cancer management and research · 2019Article
- A novel role for CAMKIIβ in the regulation of cortical neuron migration: implications for neurodevelopmental disorders.Molecular psychiatry · 2018Article
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- Olfactory receptors are expressed in pancreatic β-cells and promote glucose-stimulated insulin secretion.Scientific reports · 2018Article
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
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- Secretagogin affects insulin secretion in pancreatic β-cells by regulating actin dynamics and focal adhesion.The Biochemical journal · 2016Article
- Extracellular CADM1 interactions influence insulin secretion by rat and human islet β-cells and promote clustering of syntaxin-1.American journal of physiology. Endocrinology and metabolism · 2016Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Actin dynamics in pancreatic β-cells is involved in insulin secretion. However, the molecular mechanisms of the regulation of actin dynamics by intracellular signals in pancreatic β-cells and its role in phasic insulin secretion are largely unknown. In this study, we elucidate the regulation of actin dynamics by neuronal Wiskott-Aldrich syndrome protein (N-WASP) and cofilin in pancreatic β-cells and demonstrate its role in glucose-induced insulin secretion (GIIS). N-WASP, which promotes actin polymerization through activation of the actin nucleation factor Arp2/3 complex, was found to be activated by glucose stimulation in insulin-secreting clonal pancreatic β-cells (MIN6-K8 β-cells). Introduction of a dominant-negative mutant of N-WASP, which lacks G-actin and Arp2/3 complex-binding region VCA, into MIN6-K8 β-cells or knockdown of N-WASP suppressed GIIS, especially the second phase. We also found that cofilin, which severs F-actin in its dephosphorylated (active) form, is converted to the phosphorylated (inactive) form by glucose stimulation in MIN6-K8 β-cells, thereby promoting F-actin remodeling. In addition, the dominant-negative mutant of cofilin, which inhibits activation of endogenous cofilin, or knockdown of cofilin reduced the second phase of GIIS. However, the first phase of GIIS occurs in the G-actin predominant state, in which cofilin activity predominates over N-WASP activity. Thus, actin dynamics regulated by the balance of N-WASP and cofilin activities determines the biphasic response of GIIS.
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