ArticleThe Journal of clinical investigation2000
PAC1 receptor-deficient mice display impaired insulinotropic response to glucose and reduced glucose tolerance.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
55 citing papers in PubMed, 194 citations in OpenAlex.
- Protective Effects of PACAP in Diabetic Complications: Retinopathy, Nephropathy and Neuropathy.International journal of molecular sciences · 2025Review
- PAC1 Receptor Knockout Mice Reveal Critical Links Between ER Stress, Myelin Homeostasis, and Neurodegeneration.International journal of molecular sciences · 2025Article
- VPAC1 and VPAC2 receptors mediate tactile hindpaw hypersensitivity and carotid artery dilatation induced by PACAP38 in a migraine relevant mouse model.The journal of headache and pain · 2024Article
- PAC1 deficiency reduces chondrogenesis in atherosclerotic lesions of hypercholesterolemic ApoE-deficient mice.BMC cardiovascular disorders · 2023Article
- Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Sudden Infant Death Syndrome: A Potential Model for Investigation.International journal of molecular sciences · 2023Review
- The functional heterogeneity of PACAP: Stress, learning, and pathology.Neurobiology of learning and memory · 2023Review
- PACAP and VIP Neuropeptides' and Receptors' Effects on Appetite, Satiety and Metabolism.Biology · 2023Review
- Genome-Wide Identification of G Protein-Coupled Receptors in Ciliated Eukaryotes.International journal of molecular sciences · 2023Article
- PACInternational journal of molecular sciences · 2022Article
- Targeting VIP and PACAP Receptor Signaling: New Insights into Designing Drugs for the PACAP Subfamily of Receptors.International journal of molecular sciences · 2022Review
- Peripheral Innervation in the Regulation of Glucose Homeostasis.Trends in neurosciences · 2021Review
- Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss.Frontiers in cellular neuroscience · 2021Article
- PAC1 deficiency attenuates progression of atherosclerosis in ApoE deficient mice under cholesterol-enriched diet.Immunobiology · 2020Article
- PACAP/PAC1 Regulation of Inflammation via Catecholaminergic Neurons in a Model of Multiple Sclerosis.Journal of molecular neuroscience : MN · 2019Article
- Recent advances in vasoactive intestinal peptide physiology and pathophysiology: focus on the gastrointestinal system.F1000Research · 2019Review
- PACAP-PAC1 Receptor Activation Is Necessary for the Sympathetic Response to Acute Intermittent Hypoxia.Frontiers in neuroscience · 2019Article
- Immunomodulatory Roles of PACAP and VIP: Lessons from Knockout Mice.Journal of molecular neuroscience : MN · 2018Review
- PACAP38 and PACThe journal of headache and pain · 2018Review
- Melanocortin neurons: Multiple routes to regulation of metabolism.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Altered Circadian Food Anticipatory Activity Rhythms in PACAP Receptor 1 (PAC1) Deficient Mice.PloS one · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a ubiquitous neuropeptide of the vasoactive intestinal peptide (VIP) family that potentiates glucose-stimulated insulin secretion. Pancreatic beta cells express two PACAP receptor subtypes, a PACAP-preferring (PAC1) and a VIP-shared (VPAC2) receptor. We have applied a gene targeting approach to create a mouse lacking the PAC1 receptor (PAC1(-/-)). These mice were viable and normoglycemic, but exhibited a slight feeding hyperinsulinemia. In vitro, in the isolated perfused pancreas, the insulin secretory response to PACAP was reduced by 50% in PAC1(-/-) mice, whereas the response to VIP was unaffected. In vivo, the insulinotropic action of PACAP was also acutely reduced, and the peptide induced impairment of glucose tolerance after an intravenous glucose injection. This demonstrates that PAC1 receptor is involved in the insulinotropic action of the peptide. Moreover, PAC1(-/-) mice exhibited reduced glucose-stimulated insulin secretion in vitro and in vivo, showing that the PAC1 receptor is required to maintain normal insulin secretory responsiveness to glucose. The defective insulinotropic action of glucose was associated with marked glucose intolerance after both intravenous and gastric glucose administration. Thus, these results are consistent with a physiological role for the PAC1 receptor in glucose homeostasis, notably during food intake.
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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.