Abstract
Type 2 diabetes mellitus is characterized by insulin resistance in the liver. Insulin is not only involved in carbohydrate metabolism, it also regulates protein synthesis. This work describes the expression of proteins in the liver of a diabetic mouse and identifies the metabolic pathways involved. Twenty-week-old diabetic db/db mice were hepatectomized, after which proteins were separated by 2D-Polyacrylamide Gel Electrophoresis (2D-PAGE). Spots varying in intensity were analyzed using mass spectrometry, and biological function was assigned by the Database for Annotation, Visualization and Integrated Discovery (DAVID) software. A differential expression of 26 proteins was identified; among these were arginase-1, pyruvate carboxylase, peroxiredoxin-1, regucalcin, and sorbitol dehydrogenase. Bioinformatics analysis indicated that many of these proteins are mitochondrial and participate in metabolic pathways, such as the citrate cycle, the fructose and mannose metabolism, and glycolysis or gluconeogenesis. In addition, these proteins are related to oxidation–reduction reactions and molecular function of vitamin binding and amino acid metabolism. In conclusion, the proteomic profile of the liver of diabetic mouse db/db exhibited mainly alterations in the metabolism of carbohydrates and nitrogen. These differences illustrate the heterogeneity of diabetes in its different stages and under different conditions and highlights the need to improve treatments for this disease.
Highlights
Type 2 Diabetes Mellitus (T2DM) is one of the fastest growing diseases, currently reaching pandemic levels
Impaired insulin signaling in the liver and adipose tissue results in increased endogenous glucose production, which leads to hyperglycemia [15]
To identify the changes in protein expression associated with diabetes and obesity, we compared the expression profile of proteins in the liver of diabetic obese db/db mice versus non-diabetic mice using two-dimensional gel electrophoresis (2-DE)
Summary
Type 2 Diabetes Mellitus (T2DM) is one of the fastest growing diseases, currently reaching pandemic levels. It is conceivable that identification of deregulated pathways and networks is a fruitful approach as a starting point for the analyses of molecular mechanisms and validation of potential disease biomarkers. The liver is involved in the natural history of the ongoing epidemics of T2DM due to its participation in increased glucose production and dysregulated lipoprotein metabolism [15]. Several proteins that are exclusively or predominantly secreted from the liver are known to directly affect glucose and lipid metabolism. Impaired insulin signaling in the liver and adipose tissue results in increased endogenous glucose production, which leads to hyperglycemia [15]. The mechanisms involved in the pathophysiology of this disease have not yet been clarified, and there could be other proteins involved in this process
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