Skeletal muscle sodium glucose co-transporters in older adults with type 2 diabetes undergoing resistance training

Francisco Castaneda, Jennifer E Layne, Carmen Castaneda, Francisco Castaneda, Jennifer E Layne, Carmen Castaneda

Abstract

We examined the expression of the sodium-dependent glucose co-transporter system (hSGLT3) in skeletal muscle of Hispanic older adults with type 2 diabetes. Subjects (65+/-8 yr) were randomized to resistance training (3x/wk, n=13) or standard of care (controls, n=5) for 16 weeks. Skeletal muscle hSGLT3 and GLUT4 mRNA transcript levels were determined by real time RT-PCR. hSGLT3 transcripts increased by a factor of ten following resistance training compared to control subjects (0.10, P=0.03). There were no differences in GLUT4 mRNA expression levels between groups. Protein expression levels of these transporters were confirmed by immunohistochemistry and Western blotting. hSGLT3 after resistance exercise was found not to be co-localized with the nicotinic acetylcholine receptor. The change in hSGLT3 transcript levels in the vastus lateralis muscle was positively correlated with glucose uptake, as measured by the change in muscle glycogen stores (r=0.53, P=0.02); and with exercise intensity, as measured by the change in muscle strength (r=0.73, P=0.001). Group assignment was be the only independent predictor of hSGLT3 transcript levels, explaining 68% of its variability (P=0.01). Our data show that hSGLT3, but not GLTU4, expression was enhanced in skeletal muscle after 16 weeks of resistance training. This finding suggests that hSGLT3, an insulin-independent glucose transporter, is activated with exercise and it may play a significant role in glycemic control with muscle contraction. The hSGLT3 exact mechanism is not well understood and requires further investigation. However its functional significance regarding a reduction of glucose toxicity and improvement of insulin resistance is the subject of ongoing research.

Conflict of interest statement

Conflict of interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1
Median relative expression ratios (2-ΔΔCt) for hSGLT3 and GLUT4 transcript levels in skeletal muscle after 16 weeks of resistance training are shown for exercise (shaded bars) and control (open bars) subjects. Error bars represent SD. * P = 0.03, difference between groups.
Figure 2
Figure 2
Representative immunohystochemical staining of vastus lateralis muscle tissue (longitudinal section, 40X magnified) using specific antibodies against hSGLT3 (QIS30: yellow; A, before; and C, after 16 weeks of resistance exercise) and without primary antibody (B, before; and D, after exercise). Cell nuclei were counterstained with DAPI (blue). Scale bar is 10 μm.
Figure 3
Figure 3
Representative Western blotting for hSGLT3, GLUT4 and GAPDH are shown before and after 16 weeks of resistance exercise training.
Figure 4
Figure 4
Representative immunohystochemical staining of the vastus lateralis muscle tissue (transversal section, 40X magnified) before (1.a,b,c) and after (2.a,b,c) exercise. Specific antibodies against the nuclei were stained with DAPI (Figures “a” shown in blue), the nicotinic acetylcholine receptor gamma (Figures “b” shown in yellow), and hSGLT3 (Figures “c” shown in green).
Figure 5
Figure 5
Pearson's correlation analysis between the absolute change (delta: week 16- week 0) in the relative expression ratio (2-ΔΔCt) of hSGLT3 transcript levels and the delta in muscle glycogen stores (A) and in muscle strength (B), are shown for each subject in the resistance training (squares) and the control (triangles) group. These figures show log-transformed hSGLT3 transcript levels.
Figure 5
Figure 5
Pearson's correlation analysis between the absolute change (delta: week 16- week 0) in the relative expression ratio (2-ΔΔCt) of hSGLT3 transcript levels and the delta in muscle glycogen stores (A) and in muscle strength (B), are shown for each subject in the resistance training (squares) and the control (triangles) group. These figures show log-transformed hSGLT3 transcript levels.

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