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.
Artigo
em Inglês
| WPRIM
| ID: wpr-321458
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>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Palmitatos
/
Farmacologia
/
Fosforilação
/
Transdução de Sinais
/
Linhagem Celular
/
Inibidor Tecidual de Metaloproteinase-1
/
Fosfatidilinositol 3-Quinases
/
Células Secretoras de Insulina
/
Proteínas Proto-Oncogênicas c-akt
/
Glucose
Limite:
Animais
Idioma:
Inglês
Revista:
Chinese Medical Journal
Ano de publicação:
2011
Tipo de documento:
Artigo
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