ArticleProceedings of the National Academy of Sciences of the United States of America2010
Identification of 9-cis-retinoic acid as a pancreas-specific autacoid that attenuates glucose-stimulated insulin secretion.
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 70 papers.
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Who cites it
70 citing papers in PubMed, 117 citations in OpenAlex.
- Genetic background modulates MafADiabetologia · 2026Article
- Deep single-cell decoding of human pancreatic islets reveals T2D β-cell gene expression defects.The EMBO journal · 2026Article
- Amino acid insufficiency impairs hepatic vitamin A mobilization in mice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Vitamin A5: Evidence, Definitions, Gaps, and Future Directions.Nutrients · 2025Review
- Impact of vitamin A on aged people's cognition and Alzheimer's disease progression in an animal model.NPJ science of food · 2025Article
- Retinoic acid signaling and metabolism in heart failure.American journal of physiology. Heart and circulatory physiology · 2025Review
- Immunometabolic effects ofImmunometabolism (Cobham, Surrey) · 2024Review
- The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes.The Journal of experimental medicine · 2024Review
- Retinoid X receptor heterodimers in hepatic function: structural insights and therapeutic potential.Frontiers in pharmacology · 2024Review
- Human nutritional relevance and suggested nutritional guidelines for vitamin A5/X and provitamin A5/X.Nutrition & metabolism · 2023Review
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- All-trans retinoic acid impairs glucose-stimulated insulin secretion by activating the RXR/SREBP-1c/UCP2 pathway.Acta pharmacologica Sinica · 2022Article
- Retinoic Acid: Sexually Dimorphic, Anti-Insulin and Concentration-Dependent Effects on Energy.Nutrients · 2022Review
- Retinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a Focus on Neuropathological Involvement.Molecular neurobiology · 2022Review
- Mechanisms of Feedback Regulation of Vitamin A Metabolism.Nutrients · 2022Review
- Altered RBP1 Gene Expression Impacts Epithelial Cell Retinoic Acid, Proliferation, and Microenvironment.Cells · 2022Article
- Adapting Physiology in Functional Human Islet Organogenesis.Frontiers in cell and developmental biology · 2022Article
- Impacts of vitamin A deficiency on biological rhythms: Insights from the literature.Frontiers in nutrition · 2022Review
- Pancreatic Ductal Adenocarcinoma: New Insights into the Actions of Vitamin A.Oncology research and treatment · 2022Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The all-trans-retinoic acid (atRA) isomer, 9-cis-retinoic acid (9cRA), activates retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in vitro. RARs control multiple genes, whereas RXRs serve as partners for RARs and other nuclear receptors that regulate metabolism. Physiological function has not been determined for 9cRA, because it has not been detected in serum or multiple tissues with analytically validated assays. Here, we identify 9cRA in mouse pancreas by liquid chromatography/tandem mass spectrometry (LC/MS/MS), and show that 9cRA decreases with feeding and after glucose dosing and varies inversely with serum insulin. 9cRA reduces glucose-stimulated insulin secretion (GSIS) in mouse islets and in the rat β-cell line 832/13 within 15 min by reducing glucose transporter type 2 (Glut2) and glucokinase (GK) activities. 9cRA also reduces Pdx-1 and HNF4α mRNA expression, ∼8- and 80-fold, respectively: defects in Pdx-1 or HNF4α cause maturity onset diabetes of the young (MODY4 and 1, respectively), as does a defective GK gene (MODY2). Pancreas β-cells generate 9cRA, and mouse models of reduced β-cell number, heterozygous Akita mice, and streptozotocin-treated mice have reduced 9cRA. 9cRA is abnormally high in glucose-intolerant mice, which have β-cell hypertropy, including mice with diet-induced obesity (DIO) and ob/ob and db/db mice. These data establish 9cRA as a pancreas-specific autacoid with multiple mechanisms of action and provide unique insight into GSIS.
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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.