Potential Biomarkers Found by Protein Profiling May Provide Insight for the Macrovascular Pathogenesis of Diabetes Mellitus

Abstract

Diabetes mellitus (DM) is an alarming threat to health of mankind, yet its pathogenesis is unclear. The purpose of this study was to find potential biomarkers to serve as indicators for the pathogenesis of DM in a time course manner. Based on our previous findings that oxidative stress occurred at week 8, aorta lysate and sera of 102 streptozotocin (STZ)-induced diabetic and 85 control male Sprague-Dawley rats were obtained at the 4th, 8th and 12th week after STZ injection. The protein profiles were studied employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology in attomole sensitivity range. In the aorta, a multiple biomarker panel was discovered at the 4th week. At the 8th week, 4 biomarkers were found, while at the 12th week, 3 biomarkers were identified. In the sera, a triplet of 3 peaks and 2 biomarkers were all discovered to have 100% classification accuracy rate to differentiate the DM and control groups at all time intervals. Besides, 2 biomarkers were also found to have high classification value at week 12. Comparing the aorta and sera from DM and non-DM rats, a bundle of potential biomarkers with significant changes in peak intensities and high classification values were found. Two of the serum biomarkers matched with islet amyloid polypeptide and resistin in the SWISS-PROT knowledgebase. Validation has been conducted using immunoassay kits. These potential biomarkers may provide valuable insight on the pathogenesis of DM and macrovascular complications.

Indomethacin reverses decreased hippocampal cell proliferation in streptozotocin-induced diabetic mice

“…Diabetes increases inflammation in humans and animals (Cho et al 2006; Jain et al 2007; Lukic et al 1998; Manrique et al 2008), which results in antineurogenic effects in the hippocampus through the activation of an orchestra of proinflammatory factors (Voloboueva and Giffard 2011; Zhao et al 2008). However, the relationship between the HPA axis and inflammation is complex and bidirectional because stress hormones are responsible for changes in immunity and the immune system can affect the endocrine environment by regulating the secretion of stress hormones (Sternberg 2006).…”

Focus on Proteomics and Bioinformatics in Translational Research and Plant Research of Obesity and Diabetes

“…Panax ginseng has been used to treat diabetes [75]. The previous studies with plants have been performed to obtain potential biomarkers for the pathogenesis of diabetes and following studies were carried out by Cho [76,77] & Cho et al [78,79] to analyse antidiabetic actions of ginsenoside Re. They reported that ginsenoside Re has a significant antidiabetic action by using SELDI-TOF-MS and bioinformatics technologies simultaneously.…”

Altered expression of serum protein in ginsenoside Re-treated diabetic rats detected by SELDI-TOF MS

“…The proteins were fractionated in an 180 L anion exchange Q HyperD F 96-well filter plate (Ciphergen Biosystems Inc., Fremont, CA, USA). Proteins/peptides bound by the ion exchange beads were eluted by a pH 9 elution buffer, followed consecutively by buffers at pH 7, 5, 4, 3 and finally by an organic buffer containing isopropanol, acetonitrile and trifluoroacetic acid as described in details in our previous papers (Cho et al, 2004(Cho et al, , 2006a(Cho et al, , 2006bYip et al, 2005). This fractionation procedure significantly increases the number of protein peaks detectable from each individual sample (Fung and Enderwick, 2002).…”

“…Application details of these bioinformatic tools were described in details in our previous papers (Cho et al, 2004(Cho et al, , 2006a(Cho et al, , 2006bYip et al, 2005). Briefly, the proteinchip profiling spectra from all the serum samples were collected and analyzed by the ProteinChip Software and Biomarker Wizard.…”