Crbp1 Modulates Glucose Homeostasis and Pancreas 9-cis-retinoic Acid Concentrations
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.
Chemistry and Geology
Molecular and Cellular Biology
Kane, M. A., Folias, A. E., Pingitore, A., Perri, M., Krois, C. R., Ryu, J. Y., Cione, E., & Napoli, J. L. (2011). CrbpI modulates glucose homeostasis and pancreas 9-cis-retinoic acid concentrations. Molecular and cellular biology, 31(16), 3277–3285. https://doi.org/10.1128/MCB.05516-11
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