Insulin regulation of multiple ribonucleic acid species in human skeletal muscle in insulin-sensitive and insulin-resistant subjects.
In vivo short term (2 h) insulin-regulated gene expression was examined in skeletal muscle of persons with differing insulin sensitivities. Nine genes were analyzed by a S1 nuclease protection assay with multiple probes (multiple S1 nuclease protection assay) to allow the simultaneous examination of RNA abundances from the multiple genes. In insulin-sensitive individuals, 5 of these 9 genes were insulin responsive. RNA from the proto-oncogenes c-Ha-ras, c-myc, and c-src transiently increased 2- to 4-fold within 30 min of insulin infusion. In addition, the RNA abundance of myf-5, a muscle specific differentiation factor, increased 3-fold with a time course similar to that of c-Ha-ras, c-myc, and c-src. In contrast, type 1 protein phosphatase alpha (PPP1A) RNA levels decreased by 50% within 30 min. In insulin-resistant individuals, the RNA levels of c-Ha-ras and myf-5 did not increase, whereas c-src RNA did increase within 30 min of insulin infusion. RNA encoding c-myc transiently increased in both groups; however, this response was lower in insulin-resistant individuals than in insulin-sensitive individuals in a pattern similar to c-Ha-ras and myf-5. PPP1A RNA levels slightly increased in insulin-resistant individuals. In both insulin-sensitive and insulin-resistant persons, RNA quantities of GLUT4, c-jun, c-fos, and the insulin receptor did not change over the period of insulin infusion. However, overall RNA levels of the insulin receptor and c-jun were lower in insulin-resistant individuals.
Thompson
D B
DB
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA.
de Gregorio
M
M
Sommercorn
J
J
D000293:Adolescent; D000328:Adult; D004268:DNA-Binding Proteins; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D011905:Genes, ras; D016391:Genes, src; D051275:Glucose Transporter Type 4; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D007700:Kinetics; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism*; D051787:Myogenic Regulatory Factor 5; D012313:RNA / Q000378:metabolism*; D015719:Single-Strand Specific DNA and RNA Endonucleases; D015534:Trans-Activators
D004268:DNA-Binding Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; C497417:MYF5 protein, human; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D051787:Myogenic Regulatory Factor 5; C495692:SLC2A4 protein, human; D015534:Trans-Activators; D012313:RNA; D015719:Single-Strand Specific DNA and RNA Endonucleases