In Skeletal Muscle, Glucose Storage and Oxidation Are Differentially Impaired by the IR1152 Mutant Receptor

Gln insulin receptor (L6(1152)) featured a 31% increased glucose consumption as compared with L6 cells expressing wild-type receptors (L6(WT)). However, insulin treatment decreased glucose consumption of the mutant cells by 20% while increasing that of the L6(WT) by 30%, In the L6WT, insulin elicited a significant increase in glucose transport and GLUT1 and GLUT4 plasma membrane expression, while in the L6(1152), all of these functions were constitutively activated and not further stimulated by insulin, Similarly, glycogen content and glycogen synthase activity were increased by 80 and 125%, respectively, in the L6(1152) versus the L6(WT) and unaffected by insulin (while a 2-fold increase was measured in insulin-exposed L6(WT)), Glucose oxidation and pyruvate dehydrogenase activity were also 25% higher in the mutant compared with the L6(WT), However, in the L6(1152), both functions decreased by 35% in response to insulin (while increasing by 60 and 80%, respectively, in the L6(WT)). Similarly as in the L6(1152), in vivo, forearm glucose uptake in IR(1152) patients was 2-fold higher than in control subjects, This difference was not accounted for by higher plasma glucose levels. We conclude that, in skeletal muscle, glucose storage and oxidation are differentially impaired by the expression of IR(1152), suggesting that their regulation by insulin involves divergent signaling pathways, Muscle expression of IR(1152) may contribute to impairing glucose tolerance in IR(1152) individua -->
Popis souboru: STAMPA
ISSN: 0021-9258
Přístupová URL adresa: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c8887b5141490e3f4fbcaee32cd98cee
https://doi.org/10.1074/jbc.272.11.7290
Rights: OPEN
Přírůstkové číslo: edsair.doi.dedup.....c8887b5141490e3f4fbcaee32cd98cee
Autor: Claudia Miele, Brunella Capaldo, Gerolama Condorelli, Gabriele Riccardi, Pietro Formisano, Renata Auricchio, Francesco Beguinot, Giuseppe Bifulco, Matilde Caruso, A Oliva
Přispěvatelé: Caruso, M, Miele, C, Formisano, Pietro, Condorelli, Gerolama, Bifulco, G, Oliva, A, Auricchio, Renata, Riccardi, Gabriele, Capaldo, Brunella, Beguinot, Francesco
Rok vydání: 1997
Předmět:
Zdroj: The Journal of biological chemistry
272 (1997): 7290–7297.
info:cnr-pdr/source/autori:Caruso M, Miele C, Formisano P, Condorelli G, Bifulco G, Oliva A, Auricchio R, Riccardi G, Capaldo B, Beguinot F./titolo:In skeletal muscle, glucose storage and oxidation are differentially impaired by the IR1152 mutant receptor./doi:/rivista:The Journal of biological chemistry (Print)/anno:1997/pagina_da:7290/pagina_a:7297/intervallo_pagine:7290–7297/volume:272
ISSN: 0021-9258
Popis: L6 myotubes expressing the constitutively active Arg(1152)-->Gln insulin receptor (L6(1152)) featured a 31% increased glucose consumption as compared with L6 cells expressing wild-type receptors (L6(WT)). However, insulin treatment decreased glucose consumption of the mutant cells by 20% while increasing that of the L6(WT) by 30%, In the L6WT, insulin elicited a significant increase in glucose transport and GLUT1 and GLUT4 plasma membrane expression, while in the L6(1152), all of these functions were constitutively activated and not further stimulated by insulin, Similarly, glycogen content and glycogen synthase activity were increased by 80 and 125%, respectively, in the L6(1152) versus the L6(WT) and unaffected by insulin (while a 2-fold increase was measured in insulin-exposed L6(WT)), Glucose oxidation and pyruvate dehydrogenase activity were also 25% higher in the mutant compared with the L6(WT), However, in the L6(1152), both functions decreased by 35% in response to insulin (while increasing by 60 and 80%, respectively, in the L6(WT)). Similarly as in the L6(1152), in vivo, forearm glucose uptake in IR(1152) patients was 2-fold higher than in control subjects, This difference was not accounted for by higher plasma glucose levels. We conclude that, in skeletal muscle, glucose storage and oxidation are differentially impaired by the expression of IR(1152), suggesting that their regulation by insulin involves divergent signaling pathways, Muscle expression of IR(1152) may contribute to impairing glucose tolerance in IR(1152) individua
Databáze: OpenAIRE