Abstract

Citrate carrier (CiC), an integral protein of the mitochondrial inner membrane, plays an important role in hepatic intermediary metabolism, supplying the cytosol with acetyl-coenzyme A for fatty acid and cholesterol synthesis. Here, the effect of streptozotocin-induced diabetes on CiC activity and expression in rat liver was investigated. The rate of citrate transport was reduced by about35% in mitochondria from diabetic vs. control rats. Kinetic studies in mitochondria from diabetic rats showed a reduction inmaximumvelocity and almost unchanged Michaelis-Menten constant of the CiC protein. Mitochondrial phospholipid amount was not significantly affected, whereas an increase in the cholesterol content and in the cholesterol/phospholipid ratio was observed. To thoroughly investigate the mechanism responsible for the reduced CiC activity in the diabetic state, molecular studies were performed. Ribonuclease protection assays and Western blotting analysis indicated that both hepatic CiC mRNA accumulation and protein level decreased similarly to the CiC activity. The reducedmRNAlevelandthe lower content of the mitochondrial CiC protein, might account for the decline of CiC activity in diabetic animals. To discriminate between the role played by hyperglycemia from that of hypoinsulinemia in the reduction of CiC activity and expression, studies were conducted administrating phlorizin or insulin to streptozotocin-diabetic rats. Our data indicated that both insulin and glucose affect CiC activity and expression in diabetic rats, although they act at different regulatory steps

Autore Pugliese

• Damiano Fabrizio , Siculella Luisa , Giudetti Anna Maria

Tutti gli autori

• G. V. Gnoni , A. M. Giudetti , Elisa Mercuri , Fabrizio Damiano , Eleonora Stanca , Paola Priore , Luisa Siculella

Titolo volume/Rivista

ENDOCRINOLOGY

Anno di pubblicazione

2010

ISSN

0013-7227

ISBN

Non Disponibile

Numero di citazioni Wos

9

Ultimo Aggiornamento Citazioni

28/04/2018

Numero di citazioni Scopus

11

Ultimo Aggiornamento Citazioni

28/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile