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1 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: mliang{at}mcw.edu.
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 two weeks 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 to ~3% in the cardiac left ventricle, the renal cortex, and the retina. Similarity in transcriptome response among tissues was low, with the highest similarity being 2.2% between the 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 over-represented in the responsive genes than in the entire array. Particularly interesting cases of common or tissue-specific regulation included decorin and CD36 that were up-regulated in several tissues, and serum/glucocorticoid regulated kinase and four and a half LIM domains 2 that were up-regulated 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.
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