期刊
JOURNAL OF APPLIED PHYSIOLOGY
卷 100, 期 1, 页码 150-156出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.00988.2005
关键词
diabetes; ventricular myocyte; contraction; advanced glycation end product
资金
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R15AA013575] Funding Source: NIH RePORTER
- NIAAA NIH HHS [R15 AA-13575-01] Funding Source: Medline
Diabetic cardiomyopathy is characterized by cardiac dysfunction. This study was designed to examine the effect of benfotiamine, a lipophilic derivative of thiamine, on streptozotocin (STZ)-induced cardiac contractile dysfunction in mouse cardiomyocytes. Adult male FVB mice were made diabetic with a single injection of STZ ( 200 mg/kg ip). Fourteen days later, control and diabetic ( fasting plasma glucose > 13.9 mM) mice were put on benfotiamine therapy ( 100 mg (.) kg(-1) (.) day(-1) ip) for another 14 days. Mechanical and intracellular Ca2+ properties were evaluated in left ventricular myocytes using an IonOptix MyoCam system. The following indexes were evaluated: peak shortening ( PS), time to PS ( TPS), time to 90% relengthening ( TR90), maximal velocity of shortening/ relengthening, resting and rise of intracellular Ca2+ in response to electrical stimulus, sarcoplasmic reticulum ( SR) Ca2+ load, and intracellular Ca2+ decay rate ( tau). Two- or four-week STZ treatment led to hyperglycemia, prolonged TPS and TR90, reduced SR Ca2+ load, elevated resting intracellular Ca2+ level and prolonged tau associated with normal PS, maximal velocity of shortening/ relengthening, and intracellular Ca2+ rise in response to electrical stimulus. Benfotiamine treatment abolished prolongation in TPS, TR90, and tau, as well as reduction in SR Ca2+ load without affecting hyperglycemia and elevated resting intracellular Ca2+. Diabetes triggered oxidative stress, measured by GSH-to-GSSG ratio and formation of advanced glycation end product ( AGE) in the hearts. Benfotiamine treatment alleviated oxidative stress without affecting AGE or protein carbonyl formation. Collectively, our results indicated that benfotiamine may rescue STZ-induced cardiomyocyte dysfunction but not AGE formation in short-term diabetes.
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