Abstract
CONTEXT: Mitochondrial dysfunction has been proposed to cause insulin resistance and that might stimulate cytokine production.
OBJECTIVE: The objective of the study was to elucidate the association between mitochondrial myopathy, insulin sensitivity, and cytokine levels in muscle.
DESIGN AND SETTING: This was an experimental, controlled study in outpatients.
PARTICIPANTS: Eight overnight-fasted patients (P) with various inherited mitochondrial myopathies and eight healthy subjects (C) matched for sex, age, weight, height, and physical activity participated in the study.
INTERVENTIONS: The intervention included a 120-minute hyperinsulinemic, euglycemic clamp. Another morning, microdialysis of both vastus lateralis muscles for 4 hours, including one-legged, knee extension exercise for 30 minutes, was performed.
MAIN OUTCOME MEASURES: Glucose infusion rate during 90-120 minutes of insulin infusion was measured. Cytokine concentrations in dialysate were also measured.
RESULTS: Muscle strength, percentage fat mass, and creatine kinase in plasma did not differ between groups. The maximal oxygen uptake was 21 ± 3 (SE) (P) and 36 ± 3(C) mL/kg·min (2P < .05). Basal insulin, C-peptide, and glucagon were higher in P (55 ± 10, 980 ± 92, and 102 ± 13 pM) than in C (36 ± 12, 712 ± 98, and 44 ± 10 pM) (two-sided significance testing [2P ]< .05). The homeostasis model assessment insulin sensitivity index and glucose infusion rate (6.8 ± 1.0 vs 9.4 ± 1.3 mg/min·kg) were lower, and free fatty acids and glycerol at 120 minutes were higher in P vs C (2P < .05). Dialysate concentrations of TNF-α, IL-6, IL-8, IL-10, and monocyte chemoattractant protein-1 were higher in P vs C (2P < .05). Dialysate concentrations of these cytokines and of IL-1 receptor antagonist increased during exercise (2P < .05), identically in P and C. No differences existed in plasma cytokine concentrations.
CONCLUSIONS: In patients with a variety of mitochondrial myopathies, insulin sensitivity of muscle, adipose tissue, and pancreatic A cells is reduced, supporting that mitochondrial function influences insulin action. Furthermore, a local, low-grade inflammation of potential clinical importance exists in the muscle of these patients.
Original language | English |
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Journal | The Journal of clinical endocrinology and metabolism |
Volume | 99 |
Issue number | 10 |
Pages (from-to) | 3757-65 |
Number of pages | 9 |
ISSN | 0021-972X |
DOIs | |
Publication status | Published - Oct 2014 |
Keywords
- Adipose Tissue
- Adult
- Chemokine CCL2
- Cytokines
- Exercise
- Female
- Glucagon-Secreting Cells
- Glucose Clamp Technique
- Humans
- Hyperinsulinism
- Insulin Resistance
- Interleukin-10
- Interleukin-6
- Interleukin-8
- Male
- Middle Aged
- Mitochondria
- Mitochondrial Myopathies
- Muscle, Skeletal
- Outpatients
- Tumor Necrosis Factor-alpha