Tissue inhibitor of metalloproteinase-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1 / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 258-261, 2011.
Article
de En
| WPRIM
| ID: wpr-321458
Bibliothèque responsable:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>Glucolipotoxicity might play an important role in the β cell decompensation stage during the development of obesity-associated type 2 diabetes. Tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits matrix metalloproteinase (MMP) activity and regulates proliferation and apoptosis of a variety of cell types, including pancreatic β-cells. In the present study, we investigated whether TIMP-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1.</p><p><b>METHODS</b>INS-1 cells were incubated in normal or high glucose, with or without palmitate (0.4 mmol/L), in the presence of TIMP-1 or MMP inhibitor GM60001. In some experiments, cells were pretreated with phosphatidylinositol-3 (PI-3) kinase inhibitor, LY294002 or wortmannin. The amount of dead INS-1 cells was determined by HO342 and propidium iodide staining. Akt phosphorylation was evaluated by Western blotting analysis to investigate a possible mechanism of TIMP-1's action.</p><p><b>RESULTS</b>TIMP-1 protected INS-1 cells from glucolipotoxicity independent of MMP inhibition. TIMP-1 stimulated Akt phosphorylation. Inhibition of the PI-3 kinase pathway abolished the survival effect of TIMP-1.</p><p><b>CONCLUSION</b>TIMP-1 may counteract glucolipotoxicity induced β-cell death via a PI-3 kinase pathway.</p>
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Palmitates
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Pharmacologie
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Phosphorylation
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Transduction du signal
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Lignée cellulaire
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Inhibiteur tissulaire de métalloprotéinase-1
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Phosphatidylinositol 3-kinases
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Cellules à insuline
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Protéines proto-oncogènes c-akt
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Glucose
Limites du sujet:
Animals
langue:
En
Texte intégral:
Chinese Medical Journal
Année:
2011
Type:
Article