The tissue concentration of UDP-N-acetylglucosamine modulates the stimulatory effect of insulin on skeletal muscle glucose uptake.
J Biol Chem
; 272(8): 4889-95, 1997 Feb 21.
Article
em En
| MEDLINE
| ID: mdl-9030547
ABSTRACT
To delineate the biochemical mechanism by which increased availability of GlcN impairs insulin action on skeletal muscle glucose uptake, we replenished the uridine pool during GlcN administration. Co-infusion of uridine with GlcN prevented the GlcN-induced fall in skeletal muscle UDP-glucose levels (24.9 +/- 5. 3 versus 10.1 +/- 2.9 nmol/g; p < 0.01) and further increased the skeletal muscle UDP-GlcNAc levels (198.4 +/- 26.3 versus 96.0 +/- 8. 4 nmol/g; p < 0.01). Greater reductions in the rates of glucose infusion ( approximately 53%), glucose uptake ( approximately 43%), and glycogen synthesis ( approximately 60%) were observed with the addition of uridine. Similarly, the infusion of uridine alone markedly increased the skeletal muscle levels of both UDP-glucose (55.2 +/- 14.2 versus 17.8 +/- 6.1 nmol/g; p < 0.01) and UDP-GlcNAc (86.8 +/- 8.8 versus 35.9 +/- 8.4 nmol/g; p < 0.05) and induced marked insulin resistance. The decrease in insulin action on peripheral glucose uptake was highly correlated with the increase in skeletal muscle UDP-GlcNAc levels. Finally, immunoisolation of GLUT4-containing vesicles revealed that the rate of labeled GlcN incorporation was approximately 100-fold greater following GlcN compared with saline infusions (p < 0.01). We suggest that the marked reduction in insulin action induced by GlcN and uridine is mediated by increased accumulation of muscle UDP-N-acetylhexosamines, perhaps via altered glycosylation of protein(s) in GLUT4-containing vesicles.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Uridina Difosfato N-Acetilglicosamina
/
Músculo Esquelético
/
Glucose
/
Insulina
/
Proteínas Musculares
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos