Title

Crbp1 Modulates Glucose Homeostasis and Pancreas 9-cis-retinoic Acid Concentrations

Document Type

Article

Publication Date

8-15-2011

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.

Department

Chemistry and Geology

Print ISSN

0270-7306

Publication Title

Molecular and Cellular Biology

DOI

10.1128/MCB.05516-11

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