Proteomic and bioinformatic analysis of membrane proteome in type 2 diabetic mouse liver.
Type 2 diabetes mellitus (T2DM) is the most prevalent and serious metabolic disease affecting people worldwide. T2DM results from insulin resistance of the liver, muscle, and adipose tissue. In this study, we used proteomic and bioinformatic methodologies to identify novel hepatic membrane proteins that are related to the development of hepatic insulin resistance, steatosis, and T2DM. Using FT-ICR MS, we identified 95 significantly differentially expressed proteins in the membrane fraction of normal and T2DM db/db mouse liver. These proteins are primarily involved in energy metabolism pathways, molecular transport, and cellular signaling, and many of them have not previously been reported in diabetic studies. Bioinformatic analysis revealed that 16 proteins may be related to the regulation of insulin signaling in the liver. In addition, six proteins are associated with energy stress-induced, nine proteins with inflammatory stress-induced, and 14 proteins with endoplasmic reticulum stress-induced hepatic insulin resistance. Moreover, we identified 19 proteins that may regulate hepatic insulin resistance in a c-Jun amino-terminal kinase-dependent manner. In addition, three proteins, 14-3-3 protein beta (YWHAB), Slc2a4 (GLUT4), and Dlg4 (PSD-95), are discovered by comprehensive bioinformatic analysis, which have correlations with several proteins identified by proteomics approach. The newly identified proteins in T2DM should provide additional insight into the development and pathophysiology of hepatic steatosis and insulin resistance, and they may serve as useful diagnostic markers and/or therapeutic targets for these diseases.
Division of Life Science, Korea Basic Science Institute, Daejeon, Republic of Korea.
Gun-Hwa
GH
Kim
Edmond Changkyun
EC
Park
Sung-Ho
SH
Yun
Yeonhee
Y
Hong
Dong-Gyu
DG
Lee
Eun-Young
EY
Shin
Jongsun
J
Jung
Young Hwan
YH
Kim
Kyung-Bok
KB
Lee
Ik-Soon
IS
Jang
Zee-Won
ZW
Lee
Young-Ho
YH
Chung
Jong-Soon
JS
Choi
Chaejoon
C
Cheong
Soohyun
S
Kim
Seung Il
SI
Kim
D000818:Animals; D019295:Computational Biology / Q000379:methods*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results
D008565:Membrane Proteins; D020543:Proteome; D048031:JNK Mitogen-Activated Protein Kinases