Name: Transcription profiling by array of Mexican Americans with type II diabetes
Keywords: transcription profiling by array

Dataset Information

Transcription profiling by array of Mexican Americans with type II diabetes

ABSTRACT: Type 2 diabetes mellitus (DM) is characterized by insulin resistance and pancreatic beta-cell dysfunction. In high-risk subjects, the earliest detectable abnormality is insulin resistance in skeletal muscle. Impaired insulin-mediated signaling, gene expression, and glycogen synthesis, and accumulation of intramyocellular triglycerides have all been linked with insulin resistance, but no specific defect responsible for insulin resistance and DM has been identified in humans. To identify genes potentially important in the pathogenesis of DM, we analyzed gene expression in skeletal muscle from healthy metabolically characterized nondiabetic (family history negative and positive for DM) and diabetic Mexican-American subjects. We demonstrate that insulin resistance and DM associate with reduced expression of multiple nuclear respiratory factor-1 (NRF-1)-dependent genes encoding key enzymes in oxidative metabolism and mitochondrial function. While NRF-1 expression is decreased only in diabetic subjects, expression of both PPARg coactivator 1-alpha and -beta (PGC1-a/PPARGC1, and PGC1-b/PERC), coactivators of NRF-1 and PPARg-dependent transcription, is decreased in both diabetic subjects and family history positive nondiabetic subjects. Decreased PGC1 expression may be responsible for decreased expression of NRFdependent genes, leading to the metabolic disturbances characteristic of insulin resistance and DM. Human muscle samples were obtained from five subjects with type 2 diabetes and ten subjects without diabetes, as well as 5 aliquots from a single subject without diabetes. The subjects without diabetes were further classified as family history positive (four subjects) or family history negative (six subjects).

OTHER RELATED OMICS DATASETS IN: PRJNA126135

ORGANISM(S): Homo Sapiens

DISEASE(S): Control,Dm,Replicate Control

SUBMITTER: C. R Kahn Robert Saccone Edward Mun Kenneth Cusi Mary Elizabeth Patti Lawrence J Mandarino Ralph DeFronzo Jean Finlayson Sangeeta Kashyap Sarah Crunkhorn Maura Costello Isaac Kohane Edwin J Landaker Atul J Butte Allison B Goldfine Yoshinori Miyazaki Reachel Berria Mary E Patti

PROVIDER: E-GEOD-21340 | ArrayExpress | 2010-04-27

SECONDARY ACCESSION(S): GSE21340PRJNA126135

REPOSITORIES: GEO, ArrayExpress

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Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1.

Patti Mary Elizabeth ME Butte Atul J AJ Crunkhorn Sarah S Cusi Kenneth K Berria Rachele R Kashyap Sangeeta S Miyazaki Yoshinori Y Kohane Isaac I Costello Maura M Saccone Robert R Landaker Edwin J EJ Goldfine Allison B AB Mun Edward E DeFronzo Ralph R Finlayson Jean J Kahn C Ronald CR Mandarino Lawrence J LJ

Proceedings of the National Academy of Sciences of the United States of America 20030627 14

Type 2 diabetes mellitus (DM) is characterized by insulin resistance and pancreatic beta cell dysfunction. In high-risk subjects, the earliest detectable abnormality is insulin resistance in skeletal muscle. Impaired insulin-mediated signaling, gene expression, glycogen synthesis, and accumulation of intramyocellular triglycerides have all been linked with insulin resistance, but no specific defect responsible for insulin resistance and DM has been identified in humans. To identify genes potenti ...[more]

PMID: 12832613

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