Opposite Regulation of Insulin Sensitivity by Dietary Lipid Versus Carbohydrate Excess
| Autor: | Lene Secher Myrmel, Anne-Marie Lundsgaard, Andreas Børsting Jordy, Jørgen F. P. Wojtaszewski, Lise Madsen, Henriette Pilegaard, Louise D. Høeg, Annette K. Serup, Erik A. Richter, Bente Kiens, Kim A. Sjøberg, Andreas M. Fritzen, Jacob Jeppesen |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Glucose uptake Citric Acid Cycle 030209 endocrinology & metabolism Carbohydrate metabolism Diglycerides Young Adult 03 medical and health sciences 0302 clinical medicine Insulin resistance Internal medicine Internal Medicine medicine Humans Pyruvate Dehydrogenase (Lipoamide) Phosphorylation Muscle Skeletal Triglycerides Diacylglycerol kinase chemistry.chemical_classification biology Insulin Fatty Acids Fatty acid Carbohydrate medicine.disease Dietary Fats Insulin receptor 030104 developmental biology Endocrinology Liver chemistry biology.protein Carbohydrate Metabolism Insulin Resistance Oxidation-Reduction |
| Zdroj: | Diabetes. 66:2583-2595 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | To understand the mechanisms in lipid-induced insulin resistance, a more physiological approach is to enhance fatty acid (FA) availability through the diet. Nine healthy men ingested two hypercaloric diets (in 75% excess of habitual caloric intake) for 3 days, enriched in unsaturated FA (78 energy % [E%] fat) (UNSAT) or carbohydrates (80 E% carbohydrate) (CHO) as well as a eucaloric control diet (CON). Compared with CON, the UNSAT diet reduced whole-body and leg glucose disposal during a hyperinsulinemic-euglycemic clamp, while decreasing hepatic glucose production. In muscle, diacylglycerol (DAG) and intramyocellular triacylglycerol were increased. The accumulated DAG was sn-1,3 DAG, which is known not to activate PKC, and insulin signaling was intact. UNSAT decreased PDH-E1α protein content and increased inhibitory PDH-E1α Ser300 phosphorylation and FA oxidation. CHO increased whole-body and leg insulin sensitivity, while increasing hepatic glucose production. After CHO, muscle PDH-E1α Ser300 phosphorylation was decreased, and glucose oxidation increased. After UNSAT, but not CHO, muscle glucose-6-phosphate content was 103% higher compared with CON during the clamp. Thus, PDH-E1α expression and covalent regulation, and hence the tricarboxylic acid cycle influx of pyruvate-derived acetyl-CoA relative to β-oxidation–derived acetyl-CoA, are suggested to impact on insulin-stimulated glucose uptake. Taken together, the oxidative metabolic fluxes of glucose and FA are powerful and opposite regulators of insulin action in muscle. |
| Databáze: | OpenAIRE |
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