Intestinal Enteroendocrine Cell Signaling: Retinol-binding Protein 2 and Retinoid Actions.
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Authors
Smith, Christopher A
Miedzybrodzka, Emily L
Silvaroli, Josie A
Golczak, Marcin
Gribble, Fiona M
Reimann, Frank
Blaner, William S
Publication Date
2022-07-01Journal Title
Endocrinology
ISSN
0013-7227
Publisher
The Endocrine Society
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Calderon, R. M., Smith, C. A., Miedzybrodzka, E. L., Silvaroli, J. A., Golczak, M., Gribble, F. M., Reimann, F., & et al. (2022). Intestinal Enteroendocrine Cell Signaling: Retinol-binding Protein 2 and Retinoid Actions.. Endocrinology https://doi.org/10.1210/endocr/bqac064
Abstract
Retinol-binding protein 2-deficient (Rbp2-/-) mice are more prone to obesity, glucose intolerance, and hepatic steatosis than matched controls. Glucose-dependent insulinotropic polypeptide (GIP) blood levels are dysregulated in these mice. The present studies provide new insights into these observations. Single cell transcriptomic and immunohistochemical studies establish that RBP2 is highly expressed in enteroendocrine cells (EECs) that produce incretins, either GIP or glucagon-like peptide-1. EECs also express an enzyme needed for all-trans-retinoic acid (ATRA) synthesis, aldehyde dehydrogenase 1 family member A1, and retinoic acid receptor-alpha, which mediates ATRA-dependent transcription. Total and GIP-positive EECs are significantly lower in Rbp2-/- mice. The plasma transport protein for retinol, retinol-binding protein 4 (RBP4) is also expressed in EECs and is cosecreted with GIP upon stimulation. Collectively, our data support direct roles for RBP2 and ATRA in cellular processes that give rise to GIP-producing EECs and roles for RBP2 and RBP4 within EECs that facilitate hormone storage and secretion.
Sponsorship
Wellcome Trust (106262/Z/14/Z)
MRC (MC_UU_00014/3)
Medical Research Council (MC_UU_12012/3)
Identifiers
External DOI: https://doi.org/10.1210/endocr/bqac064
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336956
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