Phielix 2008 Diabetes
| Phielix E, Schrauwen-Hinderling VB, Mensink M, Lenaers E, Meex R, Hoeks J, Kooi ME, Moonen-Kornips E, Sels JP, Hesselink MK, Schrauwen P (2008) Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients. Diabetes 57(11): 2943-2949. |
Phielix E, Schrauwen-Hinderling VB, Mensink M, Lenaers E, Meex R, Hoeks J, Kooi ME, Moonen-Kornips E, Sels JP, Hesselink MK, Schrauwen P (2008) Diabetes
Abstract: Objective A lower in vivo mitochondrial function has been reported in (first-degree relatives (FDR) of) diabetic patients (T2DM). The nature of this reduction is unknown. Here we tested the hypothesis that a lower intrinsic mitochondrial respiratory capacity may underlie lower in vivo mitochondrial function observed in T2DM. Research Design and Methods Ten overweight T2DM, twelve FDR, and sixteen control subjects - all males - matched for age and BMI participated in this study. Insulin sensitivity was measured with a hyperinsulineamic euglyceamic clamp. Ex vivo intrinsic mitochondrial respiratory capacity was determined in permeabilized skinned muscle fibers using high-resolution respirometry and normalized for mitochondrial content. In vivo mitochondrial function was determined by measuring post-exercise PCr recovery half-time (PCrt1/2) using 31Phosphorus Magnetic Resonance Spectroscopy. Results Insulin-stimulated glucose disposal (ฮผmol/kgFFM/min) was lower in T2DM compared to control subjects (11.2 ยฑ 2.8 vs 28.9 ยฑ 3.7, respectively; p=0.003), with intermediate values for FDR (22.1 ยฑ 3.4). In vivo mitochondrial function was 25% lower in T2DM (p=0.034) and 23% lower in FDR, but the latter did not reach statistical significance (p=0.08). Interestingly, ADPstimulated basal respiration was 35% lower in T2DM (p=0.031) and FCCP-driven maximal mitochondrial respiratory capacity was 31% lower in T2DM (p=0.05) compared to control subjects with intermediate values for FDR. Conclusions A reduced basal ADP-stimulated and maximal mitochondrial respiratory capacity underlies the reduction in in vivo mitochondrial function, independent of mitochondrial content. A reduced capacity at both the level of the electron transport chain and phosphorylation system underlies this impaired mitochondrial capacity.
Labels:
Tissue;cell: Skeletal Muscle"Skeletal Muscle" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.
Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
HRR: Oxygraph-2k
