Differential proteomic analysis of the pancreas of diabetic db/db mice reveals the proteins involved in the development of complications of diabetes mellitus.

Type 2 diabetes mellitus is characterized by hyperglycemia and insulin-resistance. Diabetes results from pancreatic inability to secrete the insulin needed to overcome this resistance. We analyzed the protein profile from the pancreas of ten-week old diabetic db/db and wild type mice through proteomics. Pancreatic proteins were separated in two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and significant changes in db/db mice respect to wild type mice were observed in 27 proteins. Twenty five proteins were identified by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) and their interactions were analyzed using search tool for the retrieval of interacting genes/proteins (STRING) and database for annotation, visualization and integrated discovery (DAVID). Some of these proteins were Pancreatic α-amylase, Cytochrome b5, Lithostathine-1, Lithostathine-2, Chymotrypsinogen B, Peroxiredoxin-4, Aspartyl aminopeptidase, Endoplasmin, and others, which are involved in the metabolism of carbohydrates and proteins, as well as in oxidative stress, and inflammation. Remarkably, these are mostly endoplasmic reticulum proteins related to peptidase activity, i.e., they are involved in proteolysis, glucose catabolism and in the tumor necrosis factor-mediated signaling pathway. These results suggest mechanisms for insulin resistance, and the chronic inflammatory state observed in diabetes.

[Contributions of proteomics in the study of diabetes]. / Aportaciones de la proteómica en el estudio de la diabetes.

The incidence of type 2 diabetes mellitus (T2D) is growing rapidly due to aging, urbanization, changes in lifestyle, and increasing prevalence of obesity. In T2D, chronic hyperglycemia leads to macro and micro vascular complications, which currently are serious problem for health systems worldwide. The complexity of T2D and its complications requires study skills of high performance that provide important information in the understanding of the pathophysiology of the disease and biological pathways involved in development of T2D and its complications. In this work we describe the recent contributions of proteomics in the study of T2D and discuss its importance in the identification of therapeutic targets and biomarkers that help to improve the diagnosis of T2D, monitor the disease progression, and the development of new drugs to improve treatment and reduce its complications.