Insulin Resistance and Increased Muscle Cytokine Levels in Patients With Mitochondrial Myopathy

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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 languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number10
Pages (from-to)3757-3765
Number of pages9
ISSN0021-972X
DOIs
Publication statusPublished - 2014

    Research areas

  • 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

ID: 137748847