کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1905286 1534700 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Chronic hyperglycemia reduces substrate oxidation and impairs metabolic switching of human myotubes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Chronic hyperglycemia reduces substrate oxidation and impairs metabolic switching of human myotubes
چکیده انگلیسی

Skeletal muscle of insulin resistant individuals is characterized by lower fasting lipid oxidation and reduced ability to switch between lipid and glucose oxidation. The purpose of the present study was to examine if chronic hyperglycemia would impair metabolic switching of myotubes. Human myotubes were treated with or without chronic hyperglycemia (20 mmol/l glucose for 4 days), and metabolism of [14C]oleic acid (OA) and [14C]glucose was studied. Myotubes exposed to chronic hyperglycemia showed a significantly reduced OA uptake and oxidation to CO2, whereas acid-soluble metabolites were increased compared to normoglycemic cells (5.5 mmol/l glucose). Glucose suppressibility, the ability of acute glucose (5 mmol/l) to suppress lipid oxidation, was 50% in normoglycemic cells and reduced to 21% by hyperglycemia. Adaptability, the capacity to increase lipid oxidation with increasing fatty acid availability, was not affected by hyperglycemia. Glucose uptake and oxidation were reduced by about 40% after hyperglycemia, and oxidation of glucose in presence of mitochondrial uncouplers showed that net and maximal oxidative capacities were significantly reduced. Hyperglycemia also abolished insulin-stimulated glucose uptake. Moreover, ATP concentration was reduced by 25% after hyperglycemia. However, none of the measured mitochondrial genes were downregulated nor was mitochondrial DNA content. Microarray and real-time RT-PCR showed that no genes were significantly regulated by chronic hyperglycemia. Addition of chronic lactate reduced both glucose and OA oxidation to the same extent as hyperglycemia. In conclusion, chronic hyperglycemia reduced substrate oxidation in skeletal muscle cells and impaired metabolic switching. The effect is most likely due to an induced mitochondrial dysfunction.

Research highlights
► Chronic hyperglycemia (HG) reduced both glucose and oleic acid oxidation.
► Glucose suppressibility of oleic acid oxidation was reduced after HG.
► The maximal mitochondrial capacity was reduced by HG.
► HG treatment did not change mitochondrial content or gene expression.
► HG promoted reduced myotube content of ATP.
► The effect of HG could be mimicked by addition of lactate.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1812, Issue 1, January 2011, Pages 94–105
نویسندگان
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