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Review
. 2014 Dec;38(4):308-14.
doi: 10.1152/advan.00080.2014.

Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle

Kristin I Stanford  1 , Laurie J Goodyear  2
Affiliations
Review

Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle

Kristin I Stanford et al. Adv Physiol Educ. 2014 Dec.

Abstract

Exercise is a well-established tool to prevent and combat type 2 diabetes. Exercise improves whole body metabolic health in people with type 2 diabetes, and adaptations to skeletal muscle are essential for this improvement. An acute bout of exercise increases skeletal muscle glucose uptake, while chronic exercise training improves mitochondrial function, increases mitochondrial biogenesis, and increases the expression of glucose transporter proteins and numerous metabolic genes. This review focuses on the molecular mechanisms that mediate the effects of exercise to increase glucose uptake in skeletal muscle.

Keywords: exercise; type 2 diabetes.

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Figures

Fig. 1.
Fig. 1.
Exercise and insulin regulation of glucose transport. A proposed model for the signaling pathways mediating exercise- and insulin-induced skeletal muscle glucose transport is shown. IRS-1, insulin receptor substrate-1; PAK, p21 protein (Cdc42/Rac)-activated kinase 1; LKB1, liver kinase B1; PI3K, phosphatidylinositol 3-kinase; CaMK, Ca2+/calmodulin-dependent protein kinase; SNARK, sucrose nonfermenting AMP-dependent protein kinase (AMPK)-related kinase; NRG, neuroglian; aPKCs, atypical PKCs; GLUT, glucose transporter; TBC1D1, Tre-2/USP6, BUB2, cdc16 domain family member 1; AS160, Akt substrate of 160 kDa; CBD, calmodulin-binding domain. [Adapted from Ref. .]
Fig. 2.
Fig. 2.
Exercise restores mitochondrial function in type 2 diabetic (T2D) subjects. In vivo mitochondrial function was measured in vastus lateralis muscle and expressed as the rate constant (in s−1) before (solid bars) and after training (open bars). A high rate constant reflects high in vivo mitochondrial function. Pre- and posttraining leg extension exercise was performed at 0.5 Hz to an acoustic cue on a magnetic resonance-compatible ergometer and a weight corresponding to 60% of the predetermined maximum. Postexercise phosphocreatine (PCr) resynthesis is driven almost purely oxidatively, and the resynthesis rate reflects in vivo mitochondrial function. Data are expressed as means ± SE. #Data for T2D subjects were significantly different from those of the control (C) group. *Posttraining was significantly different from pretraining. [Adapted from Ref. .]
Fig. 3.
Fig. 3.
GLUT4 and mitochondrial markers increased after 2 wk of low-volume high-intensity interval training. A–D: 2 wk of high-intensity training increased GLUT4 protein content in skeletal muscle (A), glycemic control (average blood glucose) as measured by continuous glucose monitoring (B), citrate synthase (CS) activity (C), and mitochondrial markers in skeletal muscle (D). Pre, before training; Post, after training; NDUFA9, NADH dehydrogenase (ubiquinone) 1α subcomplex subunit 9. Values are means ± SD; n = 7. *P < 0.05. [Adapted from Ref. .]
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