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ACE inhibitors enhance insulin signaling by reducing PTP 1B protein abundance and its activity in primary skeletal muscle cells from Type 2 diabetes
Author(s) -
Wang Zhong Quan,
Zhang Xian H,
Liu Xiaotuan,
Cefalu William T
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a896-d
Subject(s) - quinapril , medicine , endocrinology , insulin , ramipril , enalapril , insulin receptor , insulin resistance , ace inhibitor , glucose uptake , angiotensin converting enzyme , diabetes mellitus , chemistry , insulin receptor substrate , blood pressure
Angiotensin converting enzyme inhibitors (ACEI) are antihypertensive agents and have been associated with increased insulin sensitivity in subjects with diabetes. However, the precise molecular mechanism by which insulin action is increased is unknown. We sought to determine the effects of ACEI on cellular insulin signaling in primary cultured human skeletal muscle. Primary culture of skeletal muscle was obtained by biopsy from subjects with type 2 diabetes. The cells were treated with or without 10 mM of Captopril, Enalapril, Quinapril or Ramipril overnight. 2‐D‐glucose uptake and protein content for insulin receptor substrate‐1 (IRS‐1) and 2 (IRS‐2), insulin receptor beta‐subunit (IR b), and protein tyrosine phosphatase 1B (PTP1B) were assessed. PTP1B activity was measured. Ramipril and Quinapril significantly increased both basal and insulin stimulated glucose uptake. In contrast, Enalapril markedly increased basal, but not insulin stimulated glucose uptake. Western blotting demonstrated that Ramipril significantly increased both IRS‐1 and IRS‐2 protein content. Enalapril and Quinapril significantly increased IRS‐1, but not IRS‐2 protein abundance. There was a trend that all ACE inhibitors increased IR bƒnprotein abundance. PTP 1B protein levels were reduced by 14%, 15%, 33.2% and 38% in Captopril, Enalapril, Quinapril (P<0.05) and Ramipril (P<0.001) treated cells when compared with controls. PTP 1B activity in cultured cells was significantly decreased by all four ACE inhibitors. We demonstrated that PTP1B plays an important role in insulin resistance and ACEI increased glucose uptake and enhanced insulin signaling by reducing PTP1B protein abundance and activity in primary cultured human skeletal muscle cells from Type 2 diabetes.