Muscle Oxidative Capacity Is a Better Predictor of Insulin Sensitivity than Lipid Status

Clinton R. Bruce, Mitchell J. Anderson, Andrew L. Carey, David G. Newman, Arend Bonen, Adamandia D. Kriketos, Gregory J. Cooney, John A. Hawley

Research output: Contribution to journalArticleResearchpeer-review

175 Citations (Scopus)

Abstract

We determined whole-body insulin sensitivity, long-chain fatty acyl coenzyme A (LCACoA) content, skeletal muscle triglyceride (TGm) 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 O2 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 TGm 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. TGm 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 β-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; β-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 TGm 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 TGm concentration or long-chain fatty acyl CoA content.

Original languageEnglish
Pages (from-to)5444-5451
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number11
DOIs
Publication statusPublished - 1 Nov 2003

Cite this

Bruce, Clinton R. ; Anderson, Mitchell J. ; Carey, Andrew L. ; Newman, David G. ; Bonen, Arend ; Kriketos, Adamandia D. ; Cooney, Gregory J. ; Hawley, John A. / Muscle Oxidative Capacity Is a Better Predictor of Insulin Sensitivity than Lipid Status. In: Journal of Clinical Endocrinology and Metabolism. 2003 ; Vol. 88, No. 11. pp. 5444-5451.
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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 (TGm) 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 O2 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 TGm 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. TGm 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 β-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; β-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 TGm 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 TGm concentration or long-chain fatty acyl CoA content.",
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Muscle Oxidative Capacity Is a Better Predictor of Insulin Sensitivity than Lipid Status. / Bruce, Clinton R.; Anderson, Mitchell J.; Carey, Andrew L.; Newman, David G.; Bonen, Arend; Kriketos, Adamandia D.; Cooney, Gregory J.; Hawley, John A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 88, No. 11, 01.11.2003, p. 5444-5451.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Muscle Oxidative Capacity Is a Better Predictor of Insulin Sensitivity than Lipid Status

AU - Bruce, Clinton R.

AU - Anderson, Mitchell J.

AU - Carey, Andrew L.

AU - Newman, David G.

AU - Bonen, Arend

AU - Kriketos, Adamandia D.

AU - Cooney, Gregory J.

AU - Hawley, John A.

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N2 - We determined whole-body insulin sensitivity, long-chain fatty acyl coenzyme A (LCACoA) content, skeletal muscle triglyceride (TGm) 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 O2 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 TGm 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. TGm 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 β-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; β-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 TGm 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 TGm concentration or long-chain fatty acyl CoA content.

AB - We determined whole-body insulin sensitivity, long-chain fatty acyl coenzyme A (LCACoA) content, skeletal muscle triglyceride (TGm) 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 O2 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 TGm 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. TGm 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 β-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; β-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 TGm 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 TGm concentration or long-chain fatty acyl CoA content.

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