Transcriptome Divergence Using Microarray Analysis for Cohen Diabetic Rat Models Reveals Distinct Signaling Pathways and Metabolism Indication Potential Novel Mechanism for the Development of Type 2 Diabetes.

The Cohen diabetic (CD) rat is a versatile animal model comprised of 2 rodent swains that manifest many of the common features of type 2 diabetes (T2D) in humans. The sensitive swain (CDs) develops diabetes within 30 days when maintained on a high sucrose/copper poor diet (HSD), whereas the resistant strain (CDr) retains normal blood glucose levels. Neither strain shows any signs of diabetes when provided regular rodent diet (RD). To further characterize the genomic and proteomic changes responsible for either resistance or predisposition to T2D, pancreatic transcriptome changes of these two strains were studied by microarray analyses using the rat expression arrays (Affymetrix). Of 1178 transcripts upregulated at least three folds, 352 transcripts have been reported to be involved in T2D-related signaling pathways or metabolisms. Such transcripts include 39 markers related to insulin signaling and several others related lipid and glucose pathways, protein modifications and proteinase inhibitors and amino acid transporters. While several of these markers have been previously reported in human diabetic patients and mouse models, others, whose role in the development of the disease remain unknown, will be analyzed further. Moreover, several proteinases and proteinase inhibitors including members of serpina family were observed as upregulated genes in Cohen diabetic resistance rats, indicating a potential novel mechanism in the development of T2D through modification of insulin signaling pathway-related proteins or related receptors. In conclusion, our analyses using the Cohen rat models could indicate novel modification mechanism involved in T2D. Quantitative analyses of individual transcripts as well as modifications of their respective proteins will determine the role of such transcripts in the development of the disease and will contribute in the selection of a handful of predictive markers for the progression or resistance of the disease. [ABSTRACT FROM AUTHOR]