Effects of high-intensity interval training and moderate-intensity continuous training on glycaemic control and skeletal muscle mitochondrial function in db/db mice

Abstract

Physical activity is known as an effective strategy for prevention and treatment of Type 2 Diabetes. The aim of this work was to compare the effects of a traditional Moderate Intensity Continuous Training (MICT) with a High Intensity Interval Training (HIIT) on glucose metabolism and mitochondrial function in diabetic mice. Diabetic db/db male mice (N = 25) aged 6 weeks were subdivided into MICT, HIIT or control (CON) group. Animals in the training groups ran on a treadmill 5 days/week during 10 weeks. MICT group ran for 80 min (0° slope) at 50-60% of maximal speed (Vmax) reached during an incremental test. HIIT group ran thirteen times 4 minutes (20° slope) at 85-90% of Vmax separated by 2-min-rest periods. HIIT lowered fasting glycaemia and HbA1c compared with CON group (p < 0.05). In all mitochondrial function markers assessed, no differences were noted between the three groups except for total amount of electron transport chain proteins, slightly increased in the HIIT group vs CON. Western blot analysis revealed a significant increase of muscle Glut4 content (about 2 fold) and higher insulin-stimulated Akt phosphorylation ratios in HIIT group. HIIT seems to improve glucose metabolism more efficiently than MICT in diabetic mice by mechanisms independent of mitochondrial adaptations.

Figure 1

Effects of 10 weeks of MICT or HIIT on fasting blood glucose (a), glycosylated haemoglobin (b), fasting serum insulin (c) and blood glucose response to ITT (d,f) and OSTT (e,g). Data are expressed as means ± SEM. *p < 0.05; **p < 0.01; *Significantly different from CON; ^$Significantly different from MICT.

Figure 2

(a) Western blot representative images. The blots were cropped and full length blots are presented in Supplementary Figure S1. (b) ETC protein content assessed by western blot. (c) p-AMPKα Thr172/total-AMPK ratio. (d) Mitofusin levels assessed by western blot. (e) mRNA expression of mitochondrial biogenesis marker genes. Data are expressed as means ± SEM. ****p < 0.0001.

Figure 3

Oxygen concentration and mass-specific oxygen flux as a function of time were recorded in a SUIT protocol with permeablised gastrocnemius. 0.02 mM palmitoyl-carnitine (Pal-C) and 2 mM malate were added in the chambers before the fibres were added. (ADP: 2.5 mM adenosine diphosphate; P: 5 mM pyruvate; S: 10 mM succinate; U: Carbonyl cyanide m-chloro phenyl hydrazine (CCCP); Rot: 0.5 µM; AmA: 2.5 µM Antimycin A). (a) Representative measurement of mitochondrial respiration. (b) Effects of MICT and HITT on mitochondrial respiration. (c) Citrate synthase and (d) β-hydroxyacyl-CoA dehydrogenase activities. Data are expressed as means ± SEM.

Figure 4

(a) Western Blot representative images. The blots were cropped and full length blots are presented in Supplementary Figure S2. (b) In soleus, phosphorylation ratios of insulin-stimulated Akt ser473/total-Akt and Akt thr 308/total-Akt. Gastrocnemius (c) and soleus (d) Glut4 content assessed by western blot. Data are expressed as means ± SEM. *p < 0.05; **p < 0.01.