ArticleMolecular endocrinology (Baltimore, Md.)2012
PI3K p110α/Akt signaling negatively regulates secretion of the intestinal peptide neurotensin through interference of granule transport.
Article in Molecular endocrinology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- The Role of Inositols in Endocrine and Neuroendocrine Tumors.Biomolecules · 2024Review
- Histone deacetylase inhibitors (HDACi) increase expression of KCa2.3 (SK3) in primary microvascular endothelial cells.American journal of physiology. Cell physiology · 2022Article
- Chasing a Breath of Fresh Air in Cystic Fibrosis (CF): Therapeutic Potential of Selective HDAC6 Inhibitors to Tackle Multiple Pathways in CF Pathophysiology.Journal of medicinal chemistry · 2022Review
- For Better or Worse: The Potential for Dose Limiting the On-Target Toxicity of PI 3-Kinase Inhibitors.Biomolecules · 2019Review
- FFAR4 Is Involved in Regulation of Neurotensin Release From Neuroendocrine Cells and Male C57BL/6 Mice.Endocrinology · 2018Article
- Article
- The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models.PloS one · 2017Article
- Article
- Activation of AMPK Stimulates Neurotensin Secretion in Neuroendocrine Cells.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Neurotensin, a novel target of Wnt/β-catenin pathway, promotes growth of neuroendocrine tumor cells.International journal of cancer · 2015Article
- Pathway modulations and epigenetic alterations in ovarian tumorbiogenesis.Journal of cellular physiology · 2014Review
- Cotargeting the PI3K and RAS pathways for the treatment of neuroendocrine tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- The inhibitory effect of PIK-75 on inflammatory mediator response induced by hydrogen peroxide in feline esophageal epithelial cells.Mediators of inflammation · 2014Article
- PI3K-AKT-mTOR-signaling and beyond: the complex network in gastroenteropancreatic neuroendocrine neoplasms.Theranostics · 2014Review
- Reduced microtubule acetylation in cystic fibrosis epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Article
- Neurotensin and its high affinity receptor 1 as a potential pharmacological target in cancer therapy.Frontiers in endocrinology · 2012Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Neurotensin (NT), an intestinal peptide secreted from N cells in the small bowel, regulates a variety of physiological functions of the gastrointestinal tract, including secretion, gut motility, and intestinal growth. The class IA phosphatidylinositol 3-kinase (PI3K) family, which comprised of p110 catalytic (α, β and δ) and p85 regulatory subunits, has been implicated in the regulation of hormone secretion from endocrine cells. However, the underlying mechanisms remain poorly understood. In particular, the role of PI3K in intestinal peptide secretion is not known. Here, we show that PI3K catalytic subunit, p110α, negatively regulates NT secretion in vitro and in vivo. We demonstrate that inhibition of p110α, but not p110β, induces NT release in BON, a human endocrine cell line, which expresses NT mRNA and produces NT peptide in a manner analogous to N cells, and QGP-1, a pancreatic endocrine cell line that produces NT peptide. In contrast, overexpression of p110α decreases NT secretion. Consistently, p110α-inhibition increases plasma NT levels in mice. To further delineate the mechanisms contributing to this effect, we demonstrate that inhibition of p110α increases NT granule trafficking by up-regulating α-tubulin acetylation; NT secretion is prevented by overexpression of HDAC6, an α-tubulin deacetylase. Moreover, ras-related protein Rab27A (a small G protein) and kinase D-interacting substrate of 220 kDa (Kidins220), which are associated with NT granules, play a negative and positive role, respectively, in p110α-inhibition-induced NT secretion. Our findings identify the critical role and novel mechanisms for the PI3K signaling pathway in the control of intestinal hormone granule transport and release.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.