title: CrbpI modulates glucose homeostasis and pancreas 9-cis-retinoic acid concentrations.
abstract: Cellular retinol-binding protein type I (CrbpI), encoded by Rpb1, serves as a chaperone of retinol homeostasis, but its physiological effects remain incompletely understood. We show here that the Rbp1(-/-) mouse has disrupted retinoid homeostasis in multiple tissues, with abnormally high 9-cis-retinoic acid (9cRA), a pancreas autacoid that attenuates glucose-stimulated insulin secretion. The Rbp1(-/-) pancreas has increased retinol and intense ectopic expression of Rpb2 mRNA, which encodes CrbpII: both would contribute to increased β-cell 9cRA biosynthesis. 9cRA in Rbp1(-/-) pancreas resists postprandial and glucose-induced decreases. Rbp1(-/-) mice have defective islet expression of genes involved in glucose sensing and insulin secretion, as well as islet α-cell infiltration, which contribute to reduced glucose-stimulated insulin secretion, high glucagon secretion, an abnormally high rate of gluconeogenesis, and hyperglycemia. A diet rich in vitamin A (as in a standard chow diet) increases pancreas 9cRA and impairs glucose tolerance. Crbp1 attenuates the negative impact of vitamin A (retinol) on glucose tolerance, regardless of the dietary retinol content. Rbp1(-/-) mice have an increased rate of fatty acid oxidation and resist obesity when fed a high-fat diet. Thus, glucose homeostasis and energy metabolism rely on Rbp1 expression and its moderation of pancreas retinol and of the autacoid 9cRA.
authors.affiliation: Nutritional Science and Toxicology, College of Natural Resources, University of California, Berkeley, California 94720, USA.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Kane
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Folias
authors.forename: Attilio
authors.initials: A
authors.lastname: Pingitore
authors.forename: Mariarita
authors.initials: M
authors.lastname: Perri
authors.forename: Charles R
authors.initials: CR
authors.lastname: Krois
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Ryu
authors.forename: Erika
authors.initials: E
authors.lastname: Cione
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Napoli
mesh_terms: D000077556:Alitretinoin; D000818:Animals; D000970:Antineoplastic Agents; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular / Q000172:deficiency / Q000502:physiology*; D014212:Tretinoin / Q000378:metabolism*; D014801:Vitamin A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D054840:Retinol-Binding Proteins, Cellular; D014801:Vitamin A; D000077556:Alitretinoin; D014212:Tretinoin; D005947:Glucose