Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients.

E. Phielix, V. Schrauwen-Hinderling, M. Mensink, E. Lenaers, R.C. Meex, J. Hoeks, M.E. Kooi, E. Kornips, J.P. Sels, M.K. Hesselink, P. Schrauwen

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Abstract

AB - 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 (PCr(t1/2)) using (31)Phosphorus Magnetic Resonance Spectroscopy. Results Insulin-stimulated glucose disposal (mu mol/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, ADP-stimulated 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
Original languageEnglish
Pages (from-to)2943-2949
JournalDiabetes
Volume57
Issue number11
DOIs
Publication statusPublished - 1 Jan 2008

Cite this

@article{b3ea814eea504dba9694af5e5f03b11b,
title = "Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients.",
abstract = "AB - 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 (PCr(t1/2)) using (31)Phosphorus Magnetic Resonance Spectroscopy. Results Insulin-stimulated glucose disposal (mu mol/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, ADP-stimulated 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",
author = "E. Phielix and V. Schrauwen-Hinderling and M. Mensink and E. Lenaers and R.C. Meex and J. Hoeks and M.E. Kooi and E. Kornips and J.P. Sels and M.K. Hesselink and P. Schrauwen",
year = "2008",
month = "1",
day = "1",
doi = "10.2337/db08-0391",
language = "English",
volume = "57",
pages = "2943--2949",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "11",

}

Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients. / Phielix, E.; Schrauwen-Hinderling, V.; Mensink, M.; Lenaers, E.; Meex, R.C.; Hoeks, J.; Kooi, M.E.; Kornips, E.; Sels, J.P.; Hesselink, M.K.; Schrauwen, P.

In: Diabetes, Vol. 57, No. 11, 01.01.2008, p. 2943-2949.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients.

AU - Phielix, E.

AU - Schrauwen-Hinderling, V.

AU - Mensink, M.

AU - Lenaers, E.

AU - Meex, R.C.

AU - Hoeks, J.

AU - Kooi, M.E.

AU - Kornips, E.

AU - Sels, J.P.

AU - Hesselink, M.K.

AU - Schrauwen, P.

PY - 2008/1/1

Y1 - 2008/1/1

N2 - AB - 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 (PCr(t1/2)) using (31)Phosphorus Magnetic Resonance Spectroscopy. Results Insulin-stimulated glucose disposal (mu mol/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, ADP-stimulated 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

AB - AB - 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 (PCr(t1/2)) using (31)Phosphorus Magnetic Resonance Spectroscopy. Results Insulin-stimulated glucose disposal (mu mol/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, ADP-stimulated 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

U2 - 10.2337/db08-0391

DO - 10.2337/db08-0391

M3 - Article

VL - 57

SP - 2943

EP - 2949

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -