ArticleProceedings of the National Academy of Sciences of the United States of America2010
CRFR1 is expressed on pancreatic beta cells, promotes beta cell proliferation, and potentiates insulin secretion in a glucose-dependent manner.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 80 citations in OpenAlex.
- Article
- Modelling the effects of human SUR1 R1420H variation on insulin secretory function using isogenic iPSC-derived pancreatic islets.Diabetologia · 2026Article
- The metabolic role of corticotropin-releasing hormone receptor 2 and its UCN peptides: emerging therapeutic potential.Skeletal muscle · 2025Review
- LD block disorder-specific pleiotropic roles of novel CRHR1 in type 2 diabetes and depression disorder comorbidity.European archives of psychiatry and clinical neuroscience · 2025Article
- Translating stress systems: corticotropin releasing factor, its receptors, and the dopamine system in nonhuman primate models.Genomic psychiatry : advancing science from genes to society · 2025Article
- Regulated and adaptive in vivo insulin secretion from islets only containing β-cells.Nature metabolism · 2024Article
- Stress and the CRH System, Norepinephrine, Depression, and Type 2 Diabetes.Biomedicines · 2024Review
- The Importance of Intra-Islet Communication in the Function and Plasticity of the Islets of Langerhans during Health and Diabetes.International journal of molecular sciences · 2024Review
- Novel corticotropin-releasing hormone receptor genes (CRHR1 and CRHR2) linkage to and association with polycystic ovary syndrome.Journal of ovarian research · 2023Article
- Chromatin accessibility differences between alpha, beta, and delta cells identifies common and cell type-specific enhancers.BMC genomics · 2023Article
- Article
- Transgenic overexpression of microRNA-30d in pancreatic beta-cells progressively regulates beta-cell function and identity.Scientific reports · 2022Article
- Urocortin3: Local inducer of somatostatin release and bellwether of beta cell maturity.Peptides · 2022Review
- Beta-Cell Adaptation to Pregnancy - Role of Calcium Dynamics.Frontiers in endocrinology · 2022Review
- The Human Islet: Mini-Organ With Mega-Impact.Endocrine reviews · 2021Review
- Genetic deficiency or pharmacological inhibition of soluble epoxide hydrolase ameliorates high fat diet-induced pancreatic β-cell dysfunction and loss.Free radical biology & medicine · 2021Article
- Paracrine regulation of insulin secretion.Diabetologia · 2020Review
- Article
- UCN2: a new candidate influencing pancreatic β-cell adaptations in pregnancy.The Journal of endocrinology · 2020Article
- Glucose homeostasis is impaired in mice deficient in the neuropeptide 26RFa (QRFP).BMJ open diabetes research & care · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Corticotropin-releasing factor (CRF), originally characterized as the principal neuroregulator of the hypothalamus-pituitary-adrenal axis, has broad central and peripheral distribution and actions. We demonstrate the presence of CRF receptor type 1 (CRFR1) on primary beta cells and show that activation of pancreatic CRFR1 promotes insulin secretion, thus contributing to the restoration of normoglycemic equilibrium. Stimulation of pancreatic CRFR1 initiates a cAMP response that promotes insulin secretion in vitro and in vivo and leads to the phosphorylation of cAMP response element binding and the induction of the expression of several immediate-early genes. Thus, the insulinotropic actions of pancreatic CRFR1 oppose the activation of CRFR1 on anterior pituitary corticotropes, leading to the release of glucocorticoids that functionally antagonize the actions of insulin. Stimulation of the MIN6 insulinoma line and primary rat islets with CRF also activates the MAPK signaling cascade leading to rapid phosphorylation of Erk1/2 in response to CRFR1-selective ligands, which induce proliferation in primary rat neonatal beta cells. Importantly, CRFR1 stimulates insulin secretion only during conditions of intermediate to high ambient glucose, and the CRFR1-dependent phosphorylation of Erk1/2 is greater with elevated glucose concentrations. This response is reminiscent of the actions of the incretins, which potentiate insulin secretion only during elevated glucose conditions. The presence of CRFR1 on beta cells adds another layer of complexity to the intricate network of paracrine and autocrine factors and their cognate receptors whose coordinated efforts can dictate islet hormone output and regulate beta cell proliferation.
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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.