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Fig. 1 | Nutrition & Metabolism

Fig. 1

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

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;

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