Yang, X., Pratley, R.E., Tokraks, S., Bogardus, C. & Permana, P.A. Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians. Diabetologia 45, 1584-1593

Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Göteborg, Sweden.
Diabetologia (Impact Factor: 6.88). 12/2002; 45(11):1584-93. DOI: 10.1007/s00125-002-0905-7
Source: PubMed

ABSTRACT 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 genes linked to insulin resistance and diabetes in Pima Indians.
We compared gene expression profiles of skeletal muscle tissues from 18 insulin-sensitive versus 17 insulin-resistant equally obese, non-diabetic Pima Indians using oligonucleotide arrays consisting of about 40,600 transcripts of known 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 Real Time PCR.
There were 185 differentially expressed transcripts by the rank sum test. The differential expressions of two out of the ten best-ranked genes were confirmed and the similar expressions of all ten worst-ranked genes were reproduced.
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 and insulin resistance serve as new diabetes susceptibility genes.

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    • "Microarray technology is a powerful tool for analyzing mRNA abundance in cells or tissues on a genome-wide scale. Microarray-based transcription profiling analysis has been applied to many types of biological inquiry (Spellman et al., 1998; Yang et al., 2002; Oberthuer et al., 2006). Identification of candidate genes is an important inquiry. "
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    • "Genes differentially expressed were those with an adjusted P-value lower or equal to 0.05. Only data supported by both analyses and with an expression ratio between virus and PBS controls with values higher than 1.5 or lower than 0.66 were used for final results (Yang et al., 2002). "
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    • "Despite differences in the type of Affymetrix Gene Chip (Affymetrix, Santa Clara, California) used, number of probes on the chip, sample size, study design, subject ethnicity, and data analysis, collectively, these studies have shown only modest differences in muscle transcripts between patients who have insulin resistance with or without T2D and healthy control subjects. Thus, in most of these studies, no single gene remained differentially expressed after correction for multiple testing [42] [43] [44] [45]. Nevertheless, these studies have shown similar changes in gene expression pattern that point to abnormalities in mitochondrial oxidative phosphorylation (OXPHOS). "
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