Resistance training to improve type 2 diabetes: working toward a prescription for the future

Abstract

The prevalence of type 2 diabetes (T2D) is rapidly increasing, and effective strategies to manage and prevent this disease are urgently needed. Resistance training (RT) promotes health benefits through increased skeletal muscle mass and qualitative adaptations, such as enhanced glucose transport and mitochondrial oxidative capacity. In particular, mitochondrial adaptations triggered by RT provide evidence for this type of exercise as a feasible lifestyle recommendation to combat T2D, a disease typically characterized by altered muscle mitochondrial function. Recently, the synergistic and antagonistic effects of combined training and Metformin use have come into question and warrant more in-depth prospective investigations. In the future, clinical intervention studies should elucidate the mechanisms driving RT-mitigated mitochondrial adaptations in muscle and their link to improvements in glycemic control, cholesterol metabolism and other cardiovascular disease risk factors in individuals with T2D.

Keywords: Mitochondrial function; Resistance training; Skeletal muscle; Type 2 diabetes.

Figures

Fig. 1

Summarizes the physiological stimuli, triggered by resistance training and the specific molecular signaling events leading to a number of beneficial adaptive responses. These multifactorial benefits induced by resistance training can either be mediated independently of an increase in muscle mass (e.g., increased key insulin signaling proteins resulting in improved insulin action, enhanced post-exercise oxygen consumption resulting in a decrease of adipose tissue mass, increased mitochondrial content positively affecting fatty acid oxidation capacity and improved glucose homeostasis due to augmented rates of glycogen synthesis). The benefits can also be associated with an increase in muscle mass (e.g., improved glycemic control via increased glucose transporter 4 protein expression, increased resting energy expenditure and metabolic demand via increased muscle protein turnover). Increased substrate oxidation during exercise can alter redox state and energy charge, signaling for activation of SIRT family members and AMPK. Downstream activation of PGC-1α and FOXO1 can promote fatty acid oxidation, mitochondrial biogenesis and increased antioxidant effects. ROS signaling during exercise can also promote mitochondrial function and bolster antioxidant defense via SOD, GPX and PRDX. Mechanical stress (e.g., contraction) during exercise triggers calcium signaling that promotes glucose uptake via GLUT4, muscle growth and differentiation via MEF2 and Akt-mTOR, and has a negative effect on the activity of FOXO family members (FOXO1, FOXO3a), minimizing autophagy and muscle atrophy. Please see text for more information. Adapted from [92]. Abbreviations: AMP: Adenosine monophosphate; AMPK: Adenosine monophosphate activated kinase; ATF: activating transcription factor; CaMK: Ca2+/calmodulin-dependent protein kinase; CREB: cAMP response element-binding protein; ERK: extracellular signal–regulated kinase; FOXO: Forkhead box protein O; GLUT4: glucose transporter 4; HDAC: Histone deacetylases; IL-6: interleukin 6; JNK: c-Jun N-terminal kinases; mTOR: mammalian target of rapamycin; MEF: myocyte enhancing factor; NAD/H+: Nicotineamide adenine dinucleotide; NRF1/2: nuclear respiratory factor 1/2; p70 S6K: ribosomal protein S6 kinase beta-1; PGC1-α: peroxisome proliferator-activated receptor gamma co-activator 1-alpha; PI3K: phosphatidylinositol-3-kinases; ROS: reactive oxygen species; SIRT: silent mating type information regulation homolog; TFAM: mitochondrial transcription factor A;

Fig. 2

Biguanides such as metformin exert their action via inhibition of complex I, mitochondrial glycerophosphate dehydrogenase and ATP synthase, thereby increasing [AMP]/[ATP] ratio, activating AMPK and increasing insulin sensitivity. ET acts in part through the same pathway, suggesting that these two stimuli could act synergistically. The effect of a RT regimen on individuals with T2D currently taking metformin and other anti-diabetic drugs remains to be determined