Tissue-specific transcriptome responses in rats with early streptozotocin-induced diabetes.

The understanding of common and tissue-specific molecular alterations in diabetes, particularly at early stages, is limited and fragmental. In the present study, we systematically compared transcriptome responses in four important diabetic target tissues in rats with 2 wk of streptozotocin (STZ)-induced diabetes. At this stage of diabetes, the skeletal muscle exhibited the highest transcriptome sensitivity to the STZ treatment with nearly 17% of the transcriptome being altered (false discovery rate, 1.6%) compared with approximately 3% in the cardiac left ventricle, renal cortex, and retina. Similarity in transcriptome response among tissues was low, with the highest similarity being 2.2% between skeletal muscle and the left ventricle. Several biological processes or cellular components, such as lipid metabolism in the left ventricle and collagen in the renal cortex, were significantly overrepresented in the responsive genes than in the entire array. Particularly interesting cases of common or tissue-specific regulation included decorin and CD36, which were upregulated in several tissues, and serum/glucocorticoid-regulated kinase and four and a half LIM domains 2, which were upregulated only in the renal cortex. Further biochemical analyses indicated that the thiol and oxidative stress pathway was altered in a tissue-specific manner at several levels including transcript abundance, content of reduced thiols, and lipid peroxidation, providing an example of the potential biological relevance of tissue-specific transcript regulation. These results provided a transcriptome-wide view of the molecular alterations across several key tissues in early diabetes. It appears that both common pathways and, perhaps more importantly, tissue-specific mechanisms are involved in the adaptation to diabetes or the initiation of diabetic complications.