title: Muscle oxidative capacity is a better predictor of insulin sensitivity than lipid status.
abstract: We determined whole-body insulin sensitivity, long-chain fatty acyl coenzyme A (LCACoA) content, skeletal muscle triglyceride (TG(m)) concentration, fatty acid transporter protein content, and oxidative enzyme activity in eight patients with type 2 diabetes (TYPE 2); six healthy control subjects matched for age (OLD), body mass index, percentage of body fat, and maximum pulmonary O(2) uptake; nine well-trained athletes (TRAINED); and four age-matched controls (YOUNG). Muscle biopsies from the vastus lateralis were taken before and after a 2-h euglycemic-hyperinsulinemic clamp. Oxidative enzyme activities, fatty acid transporters (FAT/CD36 and FABPpm), and TG(m) were measured from basal muscle samples, and total LCACoA content was determined before and after insulin stimulation. Whole-body insulin-stimulated glucose uptake was lower in TYPE 2 (P < 0.05) than in OLD, YOUNG, and TRAINED. TG(m) was elevated in TYPE 2 compared with all other groups (P < 0.05). However, both basal and insulin-stimulated skeletal muscle LCACoA content were similar. Basal citrate synthase activity was higher in TRAINED (P < 0.01), whereas beta-hydroxyacyl CoA dehydrogenase activity was higher in TRAINED compared with TYPE 2 and OLD. There was a significant relationship between the oxidative capacity of skeletal muscle and insulin sensitivity (citrate synthase, r = 0.71, P < 0.001; beta-hydroxyacyl CoA dehydrogenase, r = 0.61, P = 0.001). No differences were found in FAT/CD36 protein content between groups. In contrast, FABPpm protein was lower in OLD compared with TYPE 2 and YOUNG (P < 0.05). In conclusion, despite markedly elevated skeletal muscle TG(m) in type 2 diabetic patients and strikingly different levels of whole-body glucose disposal, both basal and insulin-stimulated LCACoA content were similar across groups. Furthermore, skeletal muscle oxidative capacity was a better predictor of insulin sensitivity than either TG(m) concentration or long-chain fatty acyl CoA content.
authors: Exercise Metabolism Group, School of Medical Sciences, RMIT University, Bundoora, Victoria 3083, Australia.
authors: Clinton R
authors: CR
authors: Bruce
authors: Mitchell J
authors: MJ
authors: Anderson
authors: Andrew L
authors: AL
authors: Carey
authors: David G
authors: DG
authors: Newman
authors: Arend
authors: A
authors: Bonen
authors: Adamandia D
authors: AD
authors: Kriketos
authors: Gregory J
authors: GJ
authors: Cooney
authors: John A
authors: JA
authors: Hawley
mesh_terms: D000328:Adult; D015415:Biomarkers; D015992:Body Mass Index; D018955:CD36 Antigens; D002352:Carrier Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000378:metabolism*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters / Q000378:metabolism; D018384:Oxidative Stress; D011237:Predictive Value of Tests; D025521:Tumor Suppressor Proteins
chemical_list: D015415:Biomarkers; D018955:CD36 Antigens; D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; D025521:Tumor Suppressor Proteins; D005947:Glucose