Protein Profiling and Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is a heterogeneous disease affecting millions of people worldwide. Both genetic and environmental factors contribute to the pathogenesis. The disease is characterized by alterations in many genes and their products. Historically, genomic alterations have mainly been studied at the transcriptional level in diabetes research. However, transcriptional changes do not always lead to altered translation, which makes it important to measure changes at the protein level. Proteomic techniques offer the possibility of measuring multiple protein alterations simultaneously.In this thesis, the proteomic technique surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) has been applied and evaluated in the context of T2DM research. Protocols for pancreatic islet and serum/plasma protein profiling and identification have been developed. In addition, the technique was used to analyze the influence of genetic background versus diabetic environment by determining serum protein profiles of individuals with normal glucose tolerance (NGT) and T2DM with or without family history of diabetes. In total thirteen serum proteins displayed different levels in serum from persons with NGT versus patients with T2DM…


Normal glucose homeostasis
Diabetes mellitus
Proteomic techniques
General considerations when using proteomics
The role of proteomics in diabetes research
Pancreas, pancreatic islets and cell lines
Blood, serum and plasma
Diabetic complications
Material and methods
Islet isolation and culture (Paper I)
Measurements of islet insulin release and oxygen tension (Paper I)
Study participants
Study participants Paper II
Study participants Paper III
Study participants Paper IV
Islet protein measurements
Islet protein profiling (Paper I)
Islet protein identification (Paper I)
Serum and plasma protein measurements (Papers II, III and IV)
Serum and plasma protein profiling
Serum and plasma protein identification
Confirming protein identities
Western blotting (Paper I)
Albumin analysis (Paper III)
Hemoglobin analysis (Paper IV)
Results and discussion
Islet protein profiling by SELDI-TOF MS (Paper I)
Evaluation of methodological aspects
Effects of oleate and glucose on islet insulin release, oxygen tension and protein profiles
Islet protein identification and verification
Serum protein profiling by SELDI-TOF MS (Paper II)
Evaluation of methodological aspects
Serum protein identification
Serum protein profiles of NGT and T2DM individuals with or with no family history of diabetes (Paper III)
Plasma protein profiles of T2DM individuals with low or high early insulin response (Paper IV)
Role of the differently displayed serum and plasma proteins in T2DM
Apolipoprotein CIII
Apolipoprotein H
Future perspectives
Swedish resumé

Author: Sundsten, Tea

Source: Uppsala University Library

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