Are substrate use during exercise and mitochondrial respiratory capacity decreased in arm and leg muscle in type 2 diabetes?

Abstract

Aim/hypothesis The aim of the study was to investigate mitochondrial function, fibre type distribution and substrate oxidation in arm and leg muscle during exercise in patients with type 2 diabetes and in obese and lean controls. Methods Indirect calorimetry was used to calculate fat and carbohydrate oxidation during both progressive arm-cranking and leg-cycling exercises. Muscle biopsies from arm and leg were obtained. Fibre type, as well as O 2 flux capacity of saponin-permeabilised muscle fibres were measured, the latter by high resolution respirometry, in patients with type 2 diabetes, age-and BMI-matched obese controls, and agematched lean controls. Results Fat oxidation was similar in the groups during either arm or leg exercise. During leg exercise at higher intensities, but not during arm exercise, carbohydrate oxidation was lower in patients with type 2 diabetes compared with the other groups. In patients with type 2 diabetes, ADP-stimulated state 3 respiration per mg muscle with parallel electron input from complex I+II was lower in m. vastus lateralis compared with obese and lean controls, whereas no differences between groups were present in m. deltoideus. A higher percentage of type IIX fibres was seen in m. vastus lateralis in patients with type 2 diabetes compared with obese and lean controls, whereas no difference was found in the deltoid muscle. Conclusions/interpretation This study demonstrates similar O 2 flux capacity, fibre type distribution and carbohydrate oxidation in arm muscle in the groups despite the presence of attenuated values in leg muscle in patients with type 2 diabetes compared with obese and lean controls.

Normal mitochondrial function and increased fat oxidation capacity in leg and arm muscles in obese humans

“…56 In contrast, we previously found higher respiration in deltoideus muscle in O compared with lean C subjects, normalized relative to CS activity. 13 In this study, we also found no reduction in mitochondrial respiration in O individuals, supporting the concept that mitochondrial function is not impaired in obesity. Acute weight loss seems to reduce skeletal muscle mitochondrial respiration, 57 but very few data are available in relation to weight loss and mitochondrial respiration in humans.…”

“…In a recent study, we demonstrated that maximal fat oxidation (MFO) was lower during exercise with the arms than with the legs in type 2 diabetics and in lean and O controls. 13 However, in O individuals, MFO occurred at similar exercise intensity during leg and arm cycling, whereas in type 2 diabetics and lean Cs, the exercise intensity at MFO was lower during arm exercise. 13 Thus, in this study, we investigated MFO in male O, PO and matched C subjects during graded ergometer exercise performed either only with the upper body (UB, arm cranking) or only with the lower extremities.…”

“…13 However, in O individuals, MFO occurred at similar exercise intensity during leg and arm cycling, whereas in type 2 diabetics and lean Cs, the exercise intensity at MFO was lower during arm exercise. 13 Thus, in this study, we investigated MFO in male O, PO and matched C subjects during graded ergometer exercise performed either only with the upper body (UB, arm cranking) or only with the lower extremities. In addition, we aimed at determining whether regional metabolic differences could be explained by differences in muscle fibre composition, enzymatic activity of b-hydroxy-acyl-CoAdehydrogenase and basal AMP-activated protein kinase (AMPK) phosphorylation or acetyl-CoA carboxylase (ACC) phosphorylation.…”

“…We applied a protocol that is a slightly modified version 13 of a detailed description given elsewhere. 25 In brief, mitochondrial function is assessed in saponin-permeabilized muscle fibres using sequential additions of substrates and inhibitors to assess the respiratory capacity of the various steps in the mitochondrial respiratory chain.…”

“…7,8 In line with this notion, there is evidence that mitochondrial oxidative capacity is decreased in skeletal muscle of O 9 and type 2 diabetic individuals, [10][11][12] although not all agree. 13 In sedentary O subjects, a moderate weight loss accompanied by an improved aerobic capacity leads to a normalization of mitochondrial oxidative capacity and insulin resistance. 14 However, when weight loss occurs in the absence of an increase in physical activity level, that is, without improvement in aerobic capacity, insulin resistance is normalized, 2,15 but muscle oxidative capacity remains unaltered.…”