Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians

Aims/hypothesis. We carried out global. transcript profiling to identify differentially expressed skeletal muscle genes in insulin resistance, a major risk factor for Type II (non-insulin-dependent) diabetes mellitus. This approach also complemented the ongoing, genomic linkage analyses to identify gees linked to insulin resistance and diabetes in Pima Indians. Methods We compared gene expression probes of skeletal muscle tissues from 18 insulin-sensitive versus 17 insulin-resistant equally obese, non-diabetic Pima Indians using oligonucleotide arrays consistmg of about 40,600 transcripts of know genes and expressed sequence tags, and analysed the results with the Wilcoxon rank sum test. We verified the mRNA expression of ten differentially (best-ranked) and ten similarly (worst-ranked) genes using quantitative Peal Tire PCR. Results. There were 185 differentially expressed transcripts by the rank sum test. The deferential expressions of two out of the ten best-raked genes were confirmed and the similar expressions of all ten worst-ranked genes were reproduced. Conclusion/interpretation. Of the 185 differentially expressed transcripts, 20 per cent were true positives and some could generate new hypotheses about the aetiology or pathophysiology of insulin resistance. Furthermore, differentially expressed genes in chromosomal regions with linkage to diabetes anti insulin resistance serve as new diabetes susceptibility genes.