Larsen 2011 Diabetologia: Difference between revisions
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|tissues=Skeletal muscle | |tissues=Skeletal muscle |
Revision as of 17:03, 14 March 2013
Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Andersen JL, Madsbad S, Worm D, Helge JW, Dela F (2011) Increased mitochondrial substrate sensitivity in skeletal muscle of patients with type 2 diabetes. Diabetologia 54: 1427-1436. |
Larsen S, Stride N, Hey-Mogensen M, Hansen CN, Andersen JL, Madsbad S, Worm D, Helge JW, Dela F (2011) Diabetologia
Abstract: 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<obese controls<lean controls). MnSOD was lower in patients than in lean controls. MHC I content was lowest in patients (37 ยฑ 11% [mean ยฑ SE] vs 53 ยฑ 6% and 56 ยฑ 4%) vs obese controls and lean controls, respectively. VO2 was highest in lean controls (40 ยฑ 3 ml min(-1) kg(-1) [mean ยฑ SE]) compared with patients (25 ยฑ 2) and obese controls (27 ยฑ 2). Mitochondrial content (citrate synthase) was higher (P < 0.05) in lean controls than in patients and obese controls. When normalised for mitochondrial content by citrate synthase, mitochondrial respiratory capacity was similar in all groups. However, the half maximal substrate concentration (C50) for Complex I was significantly lower (P = 0.03) in patients (1.1 ยฑ 0.2 mmol/l [mean ยฑ SE]) than in obese (2.0 ยฑ 0.3) and lean (1.8 ยฑ 0.3) controls. Likewise, C50 for Complex II was lower (P = 0.02) in patients (3.5 ยฑ 0.2 mmol/l [mean ยฑ SE]) than in obese controls (4.1 ยฑ 0.2), but did not differ from that in lean controls (3.8 ยฑ 0.4). Substrate sensitivity for octanoyl-carnitine did not differ between groups.
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. โข Keywords: mitochondrial function, ubstrate sensitivity, type 2 diabetes
โข O2k-Network Lab: DK Copenhagen Dela F
Labels:
Pathology: Diabetes
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: OXPHOS
HRR: Oxygraph-2k