PGRN: a novel therapeutic target and biomarker for insulin resistance and obesity identified by differential proteome analysis
Insulin resistance is a characteristic feature of obesity and type 2 diabetes. Adipose tissue is now recognized as not only an energy-storage tissue, but also an endocrine tissue that secretes a variety of bioactive substances (adipokines). Defects in adipokine secretion accompanying adipose tissue dysfunction contribute to the pathophysiology of insulin resistance and obesity.
The relationship between inflammatory process and insulin resistance has recently drawn considerable attention. For example, TNF-alpha, a proinflammatory cytokine, has been shown to contribute to the development of insulin resistance. On the other hand, glucocorticoids, which are known to have an anti-inflammatory action, also induce insulin resistance in human and animals. Dexamethasone, a glucocorticoid, has been reported to impair insulin signaling and insulin-stimulated glucose uptake in adipose tissue, liver, and skeletal muscle. Since TNF-alpha and dexamethasone both induce insulin resistance despite their opposite inflammatory properties, we reasoned that there might be a common key mediator responsible for the cellular basis of insulin resistance induced by TNF-alpha and dexamethasone.
In the present study, we searched for a novel adipokine(s) that play a key role in developing insulin resistance using 3T3-L1 adipocytes treated with TNF-alpha or dexamethasone. For this purpose, we utilized a method of differential proteome analysis based on stable isotope labeling of proteins with chemical reagent 2-nitrobenzenesulfenyl chloride (NBSCl) incorporating six 13C (13C6) or six 12C (13C0) in the tryptophan residues.
- Content Type:
- Paper
- Document Number:
- PO-CON1222E
- Product Type:
- Mass Spectrometry, MALDI-TOF Mass Spectrometry
- Keywords:
- insulin resistance, obesity, differential proteome analysis, diabetes, NBS method, Pharmaceutical, Life Science, Drug discovery, MALDI
- Language:
- English
- File Name:
- jpo312174.pdf
- File Size:
- 309kb