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 examin ed in skeletal muscle of persons with differing insulin sensitivities. Nine genes were analyzed by a S1 nuclease protection assay with multi ple probes (multiple S1 nuclease protection assay) to allow the simult aneous examination of RNA abundances from the multiple genes. In insul in-sensitive individuals, 5 of these 9 genes were insulin responsive. RNA from the proto-oncogenes c-Ha-ras, c-myc, and c-src transiently in creased 2- to 4-fold within 30 min of insulin infusion. In addition, t he RNA abundance of myf-5, a muscle specific differentiation factor, i ncreased 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 individual s, the RNA levels of c-Ha-ras and myf-5 did not increase, whereas c-sr c RNA did increase within 30 min of insulin infusion. RNA encoding c-m yc transiently increased in both groups; however, this response was lo wer in insulin-resistant individuals than in insulin-sensitive individ uals in a pattern similar to c-Ha-ras and myf-5. PPP1A RNA levels slig htly increased in insulin-resistant individuals. In both insulin-sensi tive and insulin-resistant persons, RNA quantities of GLUT4, c-jun, c- fos, and the insulin receptor did not change over the period of insuli n infusion. However, overall RNA levels of the insulin receptor and c- jun were lower in insulin-resistant individuals.