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.

CrbpI modulates glucose homeostasis and pancreas 9-cis-retinoic acid concentrations

ATTILIO PINGITORE;MARIARITA PERRI;CIONE E;
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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11770/156964
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 37
  • ???jsp.display-item.citation.isi??? 38
social impact