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Titolo:
Insulin inhibits the maturation phase of VLDL assembly via a phosphoinositide 3-kinase-mediated event
Autore:
Brown, AM; Gibbons, GF;
Indirizzi:
Univ Oxford, Metab Res Lab, Oxford Ctr Diabet Endocrinol & Metab, NuffieldDept Clin Med,Radcliffe Infirm, Oxford OX2 6HE, England Univ Oxford Oxford England OX2 6HE liffe Infirm, Oxford OX2 6HE, England
Titolo Testata:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
fascicolo: 10, volume: 21, anno: 2001,
pagine: 1656 - 1661
SICI:
1079-5642(200110)21:10<1656:IITMPO>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRIGLYCERIDE TRANSFER PROTEIN; LOW-DENSITY LIPOPROTEINS; MCA-RH7777 CELLS; RAT HEPATOCYTES; BREFELDIN-A; APOLIPOPROTEIN-B; APO-B; ENDOPLASMIC-RETICULUM; RICH LIPOPROTEIN; PHOSPHOLIPASE-D;
Keywords:
primary hepatocytes; apolipoprotein B; insulin; phosphoinositide 3-kinase; triacylglycerol;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Gibbons, GF Univ Oxford, Metab Res Lab, Oxford Ctr Diabet Endocrinol & Metab, NuffieldDept Clin Med,Radcliffe Infirm, Woodstock Rd, Oxford OX2 6HE, England Univ Oxford Woodstock Rd Oxford England OX2 6HE 6HE, England
Citazione:
A.M. Brown e G.F. Gibbons, "Insulin inhibits the maturation phase of VLDL assembly via a phosphoinositide 3-kinase-mediated event", ART THROM V, 21(10), 2001, pp. 1656-1661

Abstract

LY 294002 (80 mu mol/L), an inhibitor of phosphoinositide 3-kinase, was used to investigate the involvement of this enzyme in the insulin-mediated regulation of very low density lipoprotein (VLDL) apolipoprotein B (apoB) output from cultured rat hepatocytes. Newly synthesized apoB was pulse-labeledwith [S-35] methionine and was then allowed to assemble, via an intermediate precursor stage, into mature VLDL during subsequent chase periods. Brefeldin A (BFA, 0.2 mug/mL) was used to discriminate between the role of insulin in the regulation of the early, compared with the later, events of VLDL assembly, including apoB degradation. Insulin (78 nmol/L), when present during the pulse-labeling and subsequent chase periods, inhibited the secretion of apoB-100 and apoB-48 as VLDL by 53% and 56%, respectively. Degradationof both was concomitantly increased. Secretion of high density lipoproteinapoB, derived from VLDL precursors, was relatively unaffected under these conditions, as was the net synthesis of apoB-100 and apoB-48. The presence of BFA during the pulse-labeling period and subsequent chase period prevented the maturation of VLDL in the insulin-treated and the non-insulin-treated cells. BFA was then removed, allowing the maturation of VLDL to proceed. Removal of insulin at this stage reversed the overall inhibitory effect of insulin. Furthermore, when insulin remained present during this period, thesimultaneous presence of LY 294002 also reversed the inhibitory effect of insulin on VLDL apoB output and abolished the increase in apoB degradation. The results suggest that insulin signaling via phosphoinositide 3-kinase inhibited the maturation phase of VLDL assembly by preventing bulk lipid transfer to a VLDL precursor, thus enhancing the degradation of apoB. There was no inhibition of the conversion of newly synthesized apoB into the VLDL precursor form.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/09/20 alle ore 15:22:35