ArticleMolecular endocrinology (Baltimore, Md.)2014
Repurposing cAMP-modulating medications to promote β-cell replication.
Article in Molecular endocrinology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- A Review of Antidiabetic Medicinal Plants as a Novel Source of Phosphodiesterase Inhibitors: Future Perspective of New Challenges Against Diabetes Mellitus.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2024Review
- Antidepressants and type 2 diabetes: highways to knowns and unknowns.Diabetology & metabolic syndrome · 2023Review
- Apoptosis in Type 2 Diabetes: Can It Be Prevented? Hippo Pathway Prospects.International journal of molecular sciences · 2022Review
- TBK1 regulates regeneration of pancreatic β-cells.Scientific reports · 2020Article
- Role of Phosphodiesterase in the Biology and Pathology of Diabetes.International journal of molecular sciences · 2020Review
- αFrontiers in cell and developmental biology · 2020Article
- Generation of highly potent DYRK1A-dependent inducers of human β-Cell replication via Multi-Dimensional compound optimization.Bioorganic & medicinal chemistry · 2020Article
- Zinc-Chelating Small Molecules Preferentially Accumulate and Function within Pancreatic β Cells.Cell chemical biology · 2019Article
- Essential Roles for the Non-Canonical IκB Kinases in Linking Inflammation to Cancer, Obesity, and Diabetes.Cells · 2019Review
- Regulation of cAMP accumulation and activity by distinct phosphodiesterase subtypes in INS-1 cells and human pancreatic β-cells.PloS one · 2019Article
- Glucocorticoids and checkpoint tyrosine kinase inhibitors stimulate rat pancreatic beta cell proliferation differentially.PloS one · 2019Article
- Inhibition of TBK1/IKKε Promotes Regeneration of Pancreatic β-cells.Scientific reports · 2018Article
- CC-401 Promotes β-Cell Replication via Pleiotropic Consequences of DYRK1A/B Inhibition.Endocrinology · 2018Article
- Genetic Disruption of Adenosine Kinase in Mouse Pancreatic β-Cells Protects Against High-Fat Diet-Induced Glucose Intolerance.Diabetes · 2017Article
- Critical role for adenosine receptor A2a in β-cell proliferation.Molecular metabolism · 2016Article
- IGFBP1 increases β-cell regeneration by promoting α- to β-cell transdifferentiation.The EMBO journal · 2016Article
- A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform.Journal of visualized experiments : JoVE · 2016Article
- Extracellular acidification stimulates GPR68 mediated IL-8 production in human pancreatic β cells.Scientific reports · 2016Article
- Ca2+ influx through L-type Ca2+ channels and Ca2+-induced Ca2+ release regulate cAMP accumulation and Epac1-dependent ERK 1/2 activation in INS-1 cells.Molecular and cellular endocrinology · 2016Article
- Can exposure to environmental chemicals increase the risk of diabetes type 1 development?BioMed research international · 2015Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Loss of β-cell mass is a cardinal feature of diabetes. Consequently, developing medications to promote β-cell regeneration is a priority. cAMP is an intracellular second messenger that modulates β-cell replication. We investigated whether medications that increase cAMP stability or synthesis selectively stimulate β-cell growth. To identify cAMP-stabilizing medications that promote β-cell replication, we performed high-content screening of a phosphodiesterase (PDE) inhibitor library. PDE3, -4, and -10 inhibitors, including dipyridamole, were found to promote β-cell replication in an adenosine receptor-dependent manner. Dipyridamole's action is specific for β-cells and not α-cells. Next we demonstrated that norepinephrine (NE), a physiologic suppressor of cAMP synthesis in β-cells, impairs β-cell replication via activation of α(2)-adrenergic receptors. Accordingly, mirtazapine, an α(2)-adrenergic receptor antagonist and antidepressant, prevents NE-dependent suppression of β-cell replication. Interestingly, NE's growth-suppressive effect is modulated by endogenously expressed catecholamine-inactivating enzymes (catechol-O-methyltransferase and l-monoamine oxidase) and is dominant over the growth-promoting effects of PDE inhibitors. Treatment with dipyridamole and/or mirtazapine promote β-cell replication in mice, and treatment with dipyridamole is associated with reduced glucose levels in humans. This work provides new mechanistic insights into cAMP-dependent growth regulation of β-cells and highlights the potential of commonly prescribed medications to influence β-cell growth.
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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.