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 57:2943-9. |
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 (μmol/kgFFM/min) was lower in T2DM compared to control subjects (11.2 ± 2.8 vs 28.9 ± 3.7, respectively; p=0.003), with intermediate values for FDR (22.1 ± 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.
• O2k-Network Lab: NL Maastricht Schrauwen P
Labels:
Pathology: Diabetes
Tissue;cell: Skeletal muscle
Coupling state: OXPHOS
HRR: Oxygraph-2k
