Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate
Since the mitochondrial pyruvate dehydrogenase complex (PDC) controls the rate of carbohydrate oxidation, impairment of PDC activity mediated by high-fat intake has been advocated as a causative factor for the skeletal muscle insulin resistance, metabolic syndrome, and the onset of type 2 diabetes (...
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| Format: | Article |
| Language: | English |
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Korean Diabetes Association
2013-10-01
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| Series: | Diabetes & Metabolism Journal |
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| Online Access: | http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-37-301.pdf |
| _version_ | 1828768506947043328 |
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| author | Dumitru Constantin-Teodosiu |
| author_facet | Dumitru Constantin-Teodosiu |
| author_sort | Dumitru Constantin-Teodosiu |
| collection | DOAJ |
| description | Since the mitochondrial pyruvate dehydrogenase complex (PDC) controls the rate of carbohydrate oxidation, impairment of PDC activity mediated by high-fat intake has been advocated as a causative factor for the skeletal muscle insulin resistance, metabolic syndrome, and the onset of type 2 diabetes (T2D). There are also situations where muscle insulin resistance can occur independently from high-fat dietary intake such as sepsis, inflammation, or drug administration though they all may share the same underlying mechanism, i.e., via activation of forkhead box family of transcription factors, and to a lower extent via peroxisome proliferator-activated receptors. The main feature of T2D is a chronic elevation in blood glucose levels. Chronic systemic hyperglycaemia is toxic and can lead to cellular dysfunction that may become irreversible over time due to deterioration of the pericyte cell's ability to provide vascular stability and control to endothelial proliferation. Therefore, it may not be surprising that T2D's complications are mainly macrovascular and microvascular related, i.e., neuropathy, retinopathy, nephropathy, coronary artery, and peripheral vascular diseases. However, life style intervention such as exercise, which is the most potent physiological activator of muscle PDC, along with pharmacological intervention such as administration of dichloroacetate or L-carnitine can prove to be viable strategies for treating muscle insulin resistance in obesity and T2D as they can potentially restore whole body glucose disposal. |
| first_indexed | 2024-12-11T13:31:02Z |
| format | Article |
| id | doaj.art-1ed340ee794d46949c285d65fa2aa1fa |
| institution | Directory Open Access Journal |
| issn | 2233-6079 2233-6087 |
| language | English |
| last_indexed | 2024-12-11T13:31:02Z |
| publishDate | 2013-10-01 |
| publisher | Korean Diabetes Association |
| record_format | Article |
| series | Diabetes & Metabolism Journal |
| spelling | doaj.art-1ed340ee794d46949c285d65fa2aa1fa2022-12-22T01:05:15ZengKorean Diabetes AssociationDiabetes & Metabolism Journal2233-60792233-60872013-10-0137530131410.4093/dmj.2013.37.5.3012138Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and DichloroacetateDumitru Constantin-TeodosiuSince the mitochondrial pyruvate dehydrogenase complex (PDC) controls the rate of carbohydrate oxidation, impairment of PDC activity mediated by high-fat intake has been advocated as a causative factor for the skeletal muscle insulin resistance, metabolic syndrome, and the onset of type 2 diabetes (T2D). There are also situations where muscle insulin resistance can occur independently from high-fat dietary intake such as sepsis, inflammation, or drug administration though they all may share the same underlying mechanism, i.e., via activation of forkhead box family of transcription factors, and to a lower extent via peroxisome proliferator-activated receptors. The main feature of T2D is a chronic elevation in blood glucose levels. Chronic systemic hyperglycaemia is toxic and can lead to cellular dysfunction that may become irreversible over time due to deterioration of the pericyte cell's ability to provide vascular stability and control to endothelial proliferation. Therefore, it may not be surprising that T2D's complications are mainly macrovascular and microvascular related, i.e., neuropathy, retinopathy, nephropathy, coronary artery, and peripheral vascular diseases. However, life style intervention such as exercise, which is the most potent physiological activator of muscle PDC, along with pharmacological intervention such as administration of dichloroacetate or L-carnitine can prove to be viable strategies for treating muscle insulin resistance in obesity and T2D as they can potentially restore whole body glucose disposal.http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-37-301.pdfCarnitineDiabetes mellitus, type 2DichloroacetateDiet, high-fatExerciseGlucose disposalInflammationPeroxisome proliferator-activated receptorsStatins |
| spellingShingle | Dumitru Constantin-Teodosiu Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate Diabetes & Metabolism Journal Carnitine Diabetes mellitus, type 2 Dichloroacetate Diet, high-fat Exercise Glucose disposal Inflammation Peroxisome proliferator-activated receptors Statins |
| title | Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate |
| title_full | Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate |
| title_fullStr | Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate |
| title_full_unstemmed | Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate |
| title_short | Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate |
| title_sort | regulation of muscle pyruvate dehydrogenase complex in insulin resistance effects of exercise and dichloroacetate |
| topic | Carnitine Diabetes mellitus, type 2 Dichloroacetate Diet, high-fat Exercise Glucose disposal Inflammation Peroxisome proliferator-activated receptors Statins |
| url | http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-37-301.pdf |
| work_keys_str_mv | AT dumitruconstantinteodosiu regulationofmusclepyruvatedehydrogenasecomplexininsulinresistanceeffectsofexerciseanddichloroacetate |