Increased mitochondrial substrate sensitivity in skeletal muscle of patients with type 2 diabetes
S Larsen1, N Stride, M Hey-Mogensen
1Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, Copenhagen University, Blegdamsvej 3b, 2200 Copenhagen N, Denmark. stelar@sund.ku.dk
Aims/Hypothesis:
Mitochondrial respiration has been linked to insulin resistance. We studied mitochondrial respiratory capacity and substrate sensitivity in patients with type 2 diabetes (patients), and obese and lean control participants.
Methods:
Mitochondrial respiration was measured in permeabilised muscle fibres by respirometry. Protocols for respirometry included titration of substrates for complex I (glutamate), complex II (succinate) and both (octanoyl-carnitine). Myosin heavy chain (MHC) composition, antioxidant capacity (manganese superoxide dismutase [MnSOD]), citrate synthase activity and maximal oxygen uptake (VO2) were also determined. Insulin sensitivity was determined with the isoglycaemic-hyperinsulinaemic clamp technique.
Results:
Insulin sensitivity was different (p < 0.05) between the groups (patients
Conclusions/Interpretation:
Increased mitochondrial substrate sensitivity is seen in skeletal muscle from type 2 diabetic patients and is confined to non-lipid substrates. Respiratory capacity per mitochondrion is not decreased with insulin resistance.
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