期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 262, 期 1-2, 页码 155-163出版社
SPRINGER
DOI: 10.1023/B:MCBI.0000038231.68078.4b
关键词
contractile function; diabetes; myocyte insulin resistance; protein kinase C
类别
资金
- PHS HHS [60303, 66895] Funding Source: Medline
Increased protein kinase C (PKC) activity has been implicated in the pathogenesis of a number of diabetic complications, and high concentrations of glucose have been shown to increase PKC activity. The present study was designed to examine the role of PKC in diabetes-induced (and glucose-induced) cardiomyocyte dysfunction and insulin resistance (measured by glucose uptake). Adult rat ventricular myocytes were isolated from nondiabetic and type 1 diabetic animals (4-5 days post-streptozotocin treatment), and maintained overnight, with/without the nonspecific PKC inhibitor chelerythrine (CHEL = 1 muM). Myocyte mechanical properties were evaluated using a video edge-detection system. Basal and insulin-stimulated glucose uptake was measured with [H-3]-2-deoxyglucose. Blunted insulin-stimulated glucose uptake was apparent in diabetic myocytes, and both mechanical dysfunctions (e.g., slowed shortening/relengthening) and insulin resistance were maintained in culture, and normalized by CHEL. Cardiomyocytes isolated from nondiabetic animals were cultured in a high concentration of glucose (HG = 25.5 mM) medium, with/without CHEL. HG myocytes exhibited slowed shortening/relengthening and impaired insulin-stimulated glucose uptake compared to myocytes cultured in normal glucose (5.5 mM), and both impairments were prevented by culturing cells in CHEL. Our data support the view that PKC activation contributes to both diabetes-induced abnormal cardiomyocyte mechanics and insulin resistance, and that elevated glucose is sufficient to induce these effects.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据