Differential Proteomic Analysis of the Pancreas of Diabetic db/db Mice Reveals the Proteins Involved in the Development of Complications of Diabetes Mellitus

Abstract

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.

Proteins Differentially Expressed in the Pancreas of Hepatic Alcohol Dehydrogenase–Deficient Deer Mice Fed Ethanol For 3 Months

“…Up regulation of histone H4 by ethanol exposure could be a response towards induction of DNA repair and DNA replication required for the chromosomal stability. Down regulation of keratine type II cytoskeleton 8 or EndoA’ cytokeratin, related to structural and functional entities involved in apoptosis and carbohydrate metabolism in the pancreas, as found in the present study, has also been reported in ab/db mouse 49 . Down-regulation of transitional ER ATPase or valosin-containing protein (VCP) as found in this study could be associated with ethanol-induced ER stress as well as apoptosis 50 .…”

Compensatory Islet Response to Insulin Resistance Revealed by Quantitative Proteomics

“…Interestingly, a proteomics screen was used to address the transition from obesity to diabetes in the Zucker Fatty (ZF) and Zucker Diabetic Fatty (ZDF) rat models 9a . Finally, a two-dimensional gel electrophoresis approach was applied to identify proteomic changes in the entire pancreas derived from db/db or C57BL/6J mice challenged with high fat diet (HFD); however, a major limitation in these studies was a lack of distinction between acinar and islet cells 9d, 10 .…”

Proteomic Profiling of Liver and Plasma in Chronic Ethanol Feeding Model of Hepatic Alcohol Dehydrogenase-Deficient Deer Mice

“…Therefore, deficiency of CPS1 could cause an accumulation of ammonia in the blood resulting into neurotoxicity (Ah Mew et al, 2013; Skowrońska and Albercht, 2013). Cytochrome B5 is involved in a number of oxidative reactions and probably also in mitochondrial anabolic metabolism of fats and steroids (Perez-Vázquez et al, 2014). Contrary to an increased expression in ethanol-fed group as found in this study, cytochrome B5 is shown to be down regulated in ethanol-induced fatty liver and hepatocellular carcinoma in rat models (Newton et al, 2009; Liu et al, 2011; Fernando et al, 2013).…”