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Activation of the hexosamine biosynthesis pathway alters the balance between hypertrophy and apoptosis in cardiomyocytes from diabetic mice
Author(s) -
Shan Dan,
Marchase Richard B,
Dell'Italia Louis J,
Chatham John
Publication year - 2008
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.22.1_supplement.1226.16
Subject(s) - medicine , endocrinology , apoptosis , muscle hypertrophy , angiotensin ii , phenylephrine , diabetes mellitus , annexin , chemistry , receptor , blood pressure , biochemistry
Studies have shown that hyperglycemia blunts Angiotensin II (ANG) and phenylephrine (PE) induced cardiomyocyte hypertrophy by increased hexosamine biosynthesis pathway (HBP) flux. Therefore, we tested the hypothesis that diabetes attenuates ANG and PE induced hypertrophy and increases apoptosis due to HBP activation. Cardiomyocytes isolated from type 2 diabetic db/db mice and non‐diabetic controls were treated with 1μM ANG and 10μM PE for 24h. Both ANG and PE significantly increased expression of hypertrophy markers, atrial natriuretic peptide and alpha‐sarcomeric actin in the non‐diabetic but not the diabetic group. Apoptosis assessed by annexin‐V was significantly increased in db/db group (ANG: 30±0.5%; PE: 29±1%) compared to control group (ANG: 20±1.2%; PE: 21±0.6%). Treatment of db/db cardiomyocytes with HBP inhibitors azaserine (5μM) or Don (20μM), partially restored the hypertrophic response to ANG and PE and decreased apoptosis. Non‐diabetic cardiomyocytes incubated with high glucose medium (25mM) or glucosamine (GlcN, 5mM), to activate the HBP exhibited a decreased hypertrophic response to ANG or PE and increased apoptosis compared to normal glucose (5mM). These results suggest HBP pathway may play an important role in mediating the balance between cardiomyocyte hypertrophy and apoptosis in type 2 diabetes.