title: Pancreatic proteome profiling of type 1 diabetic mouse: Differential expression of proteins involved in exocrine function, stress response, growth, apoptosis and metabolism.
abstract: Type 1 diabetes (T1D) is a chronic autoimmune disease in which the pancreatic β-cells fail to produce insulin. In addition to such change in the endocrine function, the exocrine function of the pancreas is altered as well. To understand the molecular basis of the changes in both endocrine and exocrine pancreatic functions due to T1D, the proteome profile of the pancreas of control and diabetic mouse was compared using two dimensional gel electrophoresis (2D-GE) and the differentially expressed proteins identified by electrospray ionization liquid chromatography-tandem mass spectrometry (ESI-LC-MS/MS). Among several hundred protein spots analyzed, the expression levels of 27 protein spots were found to be up-regulated while that of 16 protein spots were down-regulated due to T1D. We were able to identify 23 up-regulated and 9 down-regulated protein spots and classified them by bioinformatic analysis into different functional categories: (i) exocrine enzymes (or their precursors) involved in the metabolism of proteins, lipids, and carbohydrates; (ii) chaperone/stress response; and (iii) growth, apoptosis, amino acid metabolism or energy metabolism. Several proteins were found to be present in multiple forms, possibly resulting from proteolysis and/or post-translational modifications. Succinate dehydrogenase [ubiquinone] flavoprotein subunit, which is the major catalytic subunit of succinate dehydrogenase (SDH), was found to be one of the proteins whose expression was increased in T1D mouse pancreata. Since altered expression of a protein can modify its functional activity, we tested and observed that the activity of SDH, a key metabolic enzyme, was increased in the T1D mouse pancreata as well. The potential role of the altered expression of different proteins in T1D associated pathology in mouse is discussed.
authors.affiliation: Keck Graduate Institute of Applied Life Sciences, Claremont, CA, USA; Department of Biology, York College, The City University of New York, Jamaica, NY, USA; Department of Chemistry, York College, The City University of New York, Jamaica, NY, USA.
authors.forename: Bulbul
authors.initials: B
authors.lastname: Chakravarti
authors.affiliation: Department of Chemistry, York College, The City University of New York, Jamaica, NY, USA.
authors.forename: Chheten
authors.initials: C
authors.lastname: Sherpa
authors.affiliation: Department of Biology, York College, The City University of New York, Jamaica, NY, USA; Department of Chemistry, York College, The City University of New York, Jamaica, NY, USA.
authors.forename: Devasrie
authors.initials: D
authors.lastname: Bose
authors.affiliation: Department of Chemistry, York College, The City University of New York, Jamaica, NY, USA.
authors.forename: Kakoli
authors.initials: K
authors.lastname: Paul Chowdhury
authors.affiliation: Department of Chemistry, York College, The City University of New York, Jamaica, NY, USA.
authors.forename: Kavita
authors.initials: K
authors.lastname: Khadar
authors.affiliation: Department of Pediatrics, University of South Florida, Tampa, FL, USA.
authors.forename: Yuan Clare
authors.initials: YC
authors.lastname: Zhang
authors.affiliation: Keck Graduate Institute of Applied Life Sciences, Claremont, CA, USA; Department of Chemistry, York College, The City University of New York, Jamaica, NY, USA. Electronic address: dchakravarti@york.cuny.edu.
authors.forename: Deb N
authors.initials: DN
authors.lastname: Chakravarti
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002853:Chromatography, Liquid; D019295:Computational Biology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D005420:Flavoproteins / Q000032:analysis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D013312:Stress, Physiological; D013385:Succinate Dehydrogenase / Q000032:analysis / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D000596:Amino Acids; D005420:Flavoproteins; D020543:Proteome; D013385:Succinate Dehydrogenase
keywords: Mouse; Proteome; Type 1 diabetes