Detection of Differential Proteomes Associated with the Development of Type 2 Diabetes in the Zucker Rat Model Using the iTRAQ Technique

다국어 초록 (Multilingual Abstract)

<P>Type 2 diabetes (T2D) is closely associated with obesity, and it arises when pancreatic β cells fail to achieve β cell compensation. However, the mechanism linking obesity, insulin resistance, and β cell failure in T2D is not fully understood. To explore this association, we carried out a differential proteomics study using the disease models of Zucker Fatty (ZF) and Zucker Diabetic Fatty (ZDF) rats as the rat models for obese/prediabetes and obese/diabetes, respectively. Differentially expressed islet proteins were identified among ZDF, ZF, and Zucker Lean (ZL, control rat) rats using three iTRAQ experiments, where three biological replicates and two technical replicates were examined to assess both the technical and biological reproducibilities. A total of 54 and 58 proteins were differentially expressed in ZDF versus ZL rats and in ZF versus ZL rats, respectively. Notably, the novel proteins involved in impaired insulin secretion (Scg2, Anxa2, and Rab10), mitochondrial dysfunction (Atp5b and Atp5l), extracellular matrix proteins (Lgal-1, Vim, and Fbn1), and microvascular ischemia (CPA1, CPA2, CPB, Cela2a, and Cela3b) were observed for the first time. With these novel proteins, our proteomics study could provide valuable clues for better understanding the underlying mechanisms associated with the dynamic transition of obesity to T2D.</P><P>The immunohistochemistry was performed to accomplish physiological relevance in Zucker rat models, showing islet hyperplasia existed in ZDF and ZF rat islets. Subsequently, differentially expressed islet proteins were identified among ZDF, ZF, and ZL rats using three iTRAQ experiments. Finally, differentially expressed proteins are grouped into 6 clusters using hierarchical clustering and manual grouping to investigate the molecular changes from obese nondiabetes to obese diabetes.</P><P><B>Graphic Abstract</B>
<IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jprobs/2011/jprobs.2011.10.issue-2/pr100759a/production/images/medium/pr-2010-00759a_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr100759a'>ACS Electronic Supporting Info</A></P>