Cited by 120Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes and associated disorders

Identification of 9- cis -retinoic acid as a pancreas-specific autacoid that attenuates glucose-stimulated insulin secretion

Open access
Kane, Maureen A., Folias, Alexandra E., Pingitore, Attilio, Perri, Mariarita, Obrochta, Kristin M., Krois, Charles R., Cione, Erika, Ryu, Joo Yeon +1 more·2010·Proceedings of the National Academy of Sciences

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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Registry

Crossref · 10.1073/pnas.1008859107

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  • 9cRA has been detected recently in pancreatic cells and found to have a function in regulating glucose-stimulated insulin secretion.

    “Note, however, that 9cRA has been detected recently in pancreatic cells and found to have a function in regulating glucose-stimulated insulin secretion ( 15 ).”

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Authors
Kane, M. A., Folias, A. E., Pingitore, A., Perri, M., Obrochta, K. M., Krois, C. R., Cione, E., Ryu, J. Y., & Napoli, J. L.
Affiliations
  • University of California, Berkeley (US)
  • University of Maryland, Baltimore (US)
Venue
Proceedings of the National Academy of Sciences
Published
2010-11-29
Volume
107
Issue
50
Pages
21884-21889
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1964543779
Cited by
120
References
55
Citations by year
2026: 4 · 2025: 4 · 2024: 6 · 2023: 3 · 2022: 10 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 9 · 2016: 5 · 2015: 10 · 2014: 15 · 2013: 7 · 2012: 13
FWCI
10.14
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Cornerstone (Minnesota State University, Mankato) (submittedVersion)
  • Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
Funders
  • Università della Calabria
  • Ministero dell'Università e della Ricerca
  • National Institutes of Health (DK061918)
  • University of California, San Francisco
  • National Institute on Alcohol Abuse and Alcoholism (R01AA017927)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK061918, R01DK047839, R01DK090522, DK 47839, T32DK061918, DK066924, F32DK066924)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
9-cis-retinoic acid, autacoids, pancreas, glucose-stimulated insulin secretion, pancreatic beta cells, retinoic acid receptor, retinoid X receptor, GLUT2, glucokinase, PDX1, HNF4α, maturity-onset diabetes of the young, Akita mice, diet-induced obesity, ob/ob mice, db/db mice, impaired glucose tolerance, beta-cell hypertrophy, islets
MeSH terms
Alitretinoin, Insulin Secretion, Animals, Antineoplastic Agents, Cell Line, Glucose, Insulin, Male, Mice, Inbred C57BL, Pancreas, Autacoids, Tretinoin, Mice, Rats

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