TY - JOUR

T1 - Regional anatomic differences in skeletal muscle mitochondrial respiration in type 2 diabetes and obesity

AU - Rabøl, R

AU - Larsen, S

AU - Højberg, P M V

AU - Almdal, T

AU - Boushel, Robert Christopher

AU - Haugaard, S B

AU - Andersen, J L

AU - Madsbad, S

AU - Dela, F

PY - 2010/2/1

Y1 - 2010/2/1

N2 - Context: Previous studies on leg skeletal musculature have demonstrated mitochondrial dysfunction associated with type 2 diabetes mellitus (T2DM), but it is not known whether mitochondrial dysfunction is present in the upper extremities. Objective: The aim of the study was to compare mitochondrial respiration and markers of mitochondrial content in skeletal muscle of arm and leg in patients with T2DM and obese control subjects. Patients: Ten patients with T2DM (age, 52.3 +/- 2.7 yr; body mass index, 30.1 +/- 1.2 kg/m(2)) (mean +/- se) were studied after a 2-wk washout period of oral antihyperglycemic agents. Ten control subjects (age, 54.3 +/- 2.8 yr; body mass index, 30.4 +/- 1.2 kg/m(2)) with normal fasting and 2-h oral glucose tolerance test blood glucose levels were also included. Main Outcome Measure: We measured mitochondrial respiration in saponin-treated skinned muscle fibers from biopsies of m. deltoideus and m. vastus lateralis using high-resolution respirometry. Results: In the arm, mitochondrial respiration and citrate synthase activity did not differ between groups, but mitochondrial respiration per milligram of muscle was significantly higher in the leg muscle of the control subjects compared to T2DM. Fiber type compositions in arm and leg muscles were not different between the T2DM and control group, and maximum rate of O(2) consumption did not differ between the groups. Conclusion: The results demonstrate that reduced mitochondrial function in T2DM is only present in the leg musculature. This novel finding suggests that mitochondrial dysfunction is not a primary defect affecting all skeletal muscle but could be related to a decreased response to locomotor muscle use in T2DM.

AB - Context: Previous studies on leg skeletal musculature have demonstrated mitochondrial dysfunction associated with type 2 diabetes mellitus (T2DM), but it is not known whether mitochondrial dysfunction is present in the upper extremities. Objective: The aim of the study was to compare mitochondrial respiration and markers of mitochondrial content in skeletal muscle of arm and leg in patients with T2DM and obese control subjects. Patients: Ten patients with T2DM (age, 52.3 +/- 2.7 yr; body mass index, 30.1 +/- 1.2 kg/m(2)) (mean +/- se) were studied after a 2-wk washout period of oral antihyperglycemic agents. Ten control subjects (age, 54.3 +/- 2.8 yr; body mass index, 30.4 +/- 1.2 kg/m(2)) with normal fasting and 2-h oral glucose tolerance test blood glucose levels were also included. Main Outcome Measure: We measured mitochondrial respiration in saponin-treated skinned muscle fibers from biopsies of m. deltoideus and m. vastus lateralis using high-resolution respirometry. Results: In the arm, mitochondrial respiration and citrate synthase activity did not differ between groups, but mitochondrial respiration per milligram of muscle was significantly higher in the leg muscle of the control subjects compared to T2DM. Fiber type compositions in arm and leg muscles were not different between the T2DM and control group, and maximum rate of O(2) consumption did not differ between the groups. Conclusion: The results demonstrate that reduced mitochondrial function in T2DM is only present in the leg musculature. This novel finding suggests that mitochondrial dysfunction is not a primary defect affecting all skeletal muscle but could be related to a decreased response to locomotor muscle use in T2DM.

KW - Arm

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Humans

KW - Leg

KW - Male

KW - Middle Aged

KW - Mitochondria, Muscle

KW - Muscle, Skeletal

KW - Oxygen Consumption

U2 - 10.1210/jc.2009-1844

DO - 10.1210/jc.2009-1844

M3 - Journal article

C2 - 20061415

VL - 95

SP - 857

EP - 863

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -