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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #199244
Title: SKELETAL MUSCLE SODIUM GLUCOSE CO-TRANSPORTERS IN OLDER ADULTS WITH TYPE 2 DIABETES UNDERGOING RESISTANCE TRAINING

Author
item CASTANEDA, FRANCISCO - MAX PLANK INST, GERMANY
item LAYNE, JENNIFER - TUFTS/HNRCA
item CASTANEDA, CARMEN - TUFTS/HNRCA

Submitted to: International Journal of Medical Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/16/2006
Publication Date: 5/17/2006
Citation: Castaneda, F., Layne, J., Castaneda, C. 2006. Skeletal muscle sodium glucose co-transporters in older adults with type 2 diabetes undergoing resistance training. International Journal of Medical Sciences. 3(3):84-91.

Interpretive Summary: Diabetes mellitus has a high incidence worldwide. Approximately 90-95% of people who are diagnosed with diabetes have type 2 diabetes. It results from insulin resistance and/or deficiency leading to hyperglycemia due to altered glucose transport into the cells. Cellular glucose uptake requires transport proteins that are divided in two groups: glucose facilitated transporters (GLUT) and sodium dependent D-glucose co-transporters (SGLT). GLUT allows transport of glucose down its concentration gradient, while SGLT transports glucose against its concentration gradient. The SGLT co-transport system is mainly expressed in skeletal muscle and represents an insulin-independent form of glucose uptake. Currently, there are no studies investigating the association between the expression of SGLT3 and exercise. Therefore, we investigated whether older adults with uncontrolled diabetes (poor glycemic control and sustained hyperglycemia) engaged in resistance exercise training for 16 weeks, would exhibit improved glycemic control associated with enhanced expression and synthesis of SGLT3 in skeletal muscle. If in fact exercise training increases SGLT-mediated glucose transport, the novel findings of this investigation would provide preliminary information on a possible physiological target to be studied further for the management of type 2 diabetes. We found that individuals with uncontrolled type 2 diabetes (characterized by poor glycemic control and sustained hyperglycemia), undergoing moderate to high intensity resistance exercise training for 16 weeks, exhibit a significant increase in sodium-dependent D-glucose co-transporter (SGLT3) transcript and protein levels in skeletal muscle tissue. To our knowledge, this is the first study to examine the associations between SGLT3 expression and glycemic control in human subjects subjected to resistance exercise training. A concomitant increase in glucose disposal (muscle glycogen stores) and muscle strength were observed with resistance training. Moreover, the observed increase expression in SGLT3 was significantly associated with improved glycemic control and functional capacity. Although the results of this investigation are preliminary, they suggest a possible mechanism for an exercise-mediated glucose transport system through SGLT. Given the rising prevalence of diabetes worldwide, regulation of glucose disposal through activation of the SGLT3 glucose transport system may represent an important alternative approach to effectively manage diabetes and prevent its long term complications.

Technical Abstract: We examined the expression of the sodium-dependent glucose co-transporter system (SGLT3) 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 SGLT3 and GLUT4 mRNA transcript levels were determined by real time RT-PCR. SGLT3 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. SGLT after resistance exercise was found not be co-localized with the nicotinic acetylcholine receptor. The change in SGLT3 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 SGLT3 transcript levels, explaining 68% of its variability (P=0.01). Our data show that SGLT3, but not GLTU4, expression was enhanced in human skeletal muscle after 16 weeks of resistance training. This finding suggests that SGLT3, an insulin-independent glucose transporter, is activated with exercise and it may play a significant role on glycemic control with muscle contraction. The SGLT 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.