Effect of benzyl succinate on insulin receptor function and insulin action in skeletal muscle: further evidence for a lack of spare high-affinity insulin receptors.
Benzyl succinate inhibited insulin binding and tyrosine receptor kinase in a concentration-dependent manner in the partially purified insulin receptor preparation from rat skeletal muscle. Benzyl succinate lowered the apparent number of high-affinity insulin binding sites. We have made use of the inhibitory effect of benzyl succinate to investigate the possible presence of spare high-affinity insulin receptors in muscle. Benzyl succinate inhibited the effect of a supramaximal concentration of insulin on 3-O-methylglucose uptake, 2-(methylamino)isobutyric acid uptake and lactate production by the incubated muscle. Furthermore, the inhibitory effect of benzyl succinate on insulin binding in vitro closely correlated with its inhibitory effect on insulin action in vivo. These findings suggest the absence of spare high-affinity insulin receptors in skeletal muscle. In contrast to data obtained in skeletal muscle, benzyl succinate did not affect the maximally insulin-stimulated glucose transport, although it caused a marked decrease in insulin sensitivity in isolated rat adipocytes, for which the existence of spare insulin receptors is well documented.
Gumà
A
A
Departament de Bioquímica i Fisiologia, Facultat de Biologia, Universitat de Barcelona, Spain.
Viñals
F
F
Camps
M
M
Lizarbe
M
M
Mora
C
C
Bertran
J
J
Testar
X
X
Palacín
M
M
Zorzano
A
A
D019325:3-O-Methylglucose; D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000378:metabolism; D000818:Animals; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology*; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000187:drug effects / Q000502:physiology*; D013386:Succinates / Q000494:pharmacology*
D007328:Insulin; D007329:Insulin Antagonists; D007773:Lactates; D008757:Methylglucosides; D013386:Succinates; D019325:3-O-Methylglucose; D019344:Lactic Acid; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C000249:benzylsuccinic acid; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin