Title

Short-Term Exercise Training Stimulates Mitochondrial Function in Insulin Sensitive Humans (CON) but not in First-degree Relatives (REL) of Type-2 Diabetics.

Authors

Kacerovsky, Gertrud; Chmelik, Marek; Szendroedi, Julia; Pokan, Rochus; Farukuoye, Michaela; Gruber, Stefan; Brehm, Attila; Nowotny, Peter; Schmid, Albrecht I.; Moser, Ewald; Trattnig, Siegfried; Pacini, Giovanni; Smekal, Gerhard; Roden, Michael

Abstract

REL feature impaired glucose transport which relates to reduced myocellular ATP synthesis (fATP). We hypothesized that exercise stimulates fATP, decreases intramyocellular lipids (IMCL) and so improves insulin action. Glucose tolerant REL (4f/6m, age: 39±4a, BMI: 24±lkg/m²) and CON (4f/6m, 38±4a, 24±1 kg/m²) with comparable O2[sub 2] uptake at respiratory compensation (VO[sub 2]rcp; REL:25±2, CON:26±1ml.kg[sup -1].min[sup -1];ns) underwent OGTT to measure insulin sensitivity (OGIS) and ¹H/[sup 31]P MR spectroscopy to assess IMCL and ATP synthesis from P-creatine (fPCR) and inorganic phosphate (fATP). Both tests were done before and after 1-week cycling training (2x40 min, 90% VO[sub 2]rcp). OGIS (ml.min[sup -1].m[sup -2]) was 13% lower in REL (370±20 vs 424±8;P<.05) without changes alter exercise. Basal fATP was similar but exercise increased fATP by 20% in CON (P=10[sup -4]) being 21% higher than in REL (12±1 vs 15±2µmol.ml[sup -1] min[sup -1]; P<.05). Basal fATP/fPCR ratios were 23% higher in REL (30±2, 36±2;P=.02) and decreased (P<.005) being comparable after exercise as was IMCL. VO[sub 2]max and VO[sub 2]rcp correlated with fATP (R=.617, P=.004; R=.748; P=10[sup -4]) with VO[sub 2]max independently explaining 40% (P=.004) of fATP variation. Short-term exercise training increases ATP synthesis despite unchanged insulin sensitivity in CON suggesting that stimulation of mitochondrial function precedes training effects on insulin sensitivity. In REL, impaired ATP synthesis remains despite exercise-induced normalization of the equilibrium of energy generating processes supporting the concept of inherited mitochondrial dysfunction beyond reduced mitochondrial contents.

Subjects

EXERCISE physiology; PHYSICAL fitness; MITOCHONDRIA; INSULIN; TYPE 2 diabetes; PEOPLE with diabetes

Publication

Diabetes, 2007, Vol 56, pA283

ISSN

0012-1797

Publication type

Academic Journal