The primary mechanism for decreased IR with exercise is increased skeletal muscle insulin sensitivity (18). Skeletal muscle accounts for approximately 75–95% of whole-body glucose disposal (4). Therefore, maintaining insulin sensitivity of skeletal muscle is crucial to prevent IR from progressing to T2D. Insulin sensitivity typically is greatly enhanced after a single exercise bout (3). However, a recent study in rodents showed that 29–53 hours after exercise, insulin sensitivity reverts to levels similar to sedentary controls (11). Even in nonexercising humans, 2 weeks of reduced physical activity has been shown to result in reduced insulin sensitivity (10). The quick reversal of insulin sensitivity after exercise cessation indicates the need for consistent exercise. This is a major reason why exercise guidelines for T2D suggest a maximum of 48 hours between exercise bouts (1). However, another study showed that after 8 months of exercise training, a 2-week hiatus resulted in insulin sensitivity that was still 30% higher than sedentary controls (3). Therefore, consistent exercise training may have some long-term benefits. This could potentially include increased muscle mass and therefore increased glucose uptake.
In addition to increased insulin sensitivity, exercise increases glucose uptake through muscle contraction. One potential mechanism of contraction-mediated glucose uptake involves adenosine monophosphate–activated protein kinase (AMPK). Adenosine monophosphate is elevated during low cellular energy state causing an increase in AMPK activity, ultimately leading to translocation of glucose transporters to the cell surface (8). Under basal conditions, insulin-dependent glucose transporters (GLUT4) reside intracellularly. On stimulation, GLUT4 is translocated to the membrane to facilitate glucose uptake. After exercise, glucose transporters remain at the cell surface for several hours, contributing to an increased glucose disposal during this time (7). Insulin and muscle contraction have an additive effect on lowering blood glucose, suggesting that these pathways act independently (7,8). Therefore, exercise may increase glucose disposal in persons with IR.
Another goal of exercise training is to preserve pancreatic β-cell function. β-Cells are responsible for making and releasing insulin. The elevated blood insulin level associated with IR results in premature loss of β-cell function. The Studies of Targeted Risk Reduction Interventions through Defined Exercise (STRRIDE) study indicated that overweight individuals with dyslipidemia had only approximately 50–70% β-cell function of healthy individuals in other studies (16). Fortunately, β-cell function can be enhanced through exercise. Participants in 1 studied experienced a 31% improvement in β-cell function after only 7 days of moderate-intensity aerobic exercise (5). The fact that these changes occurred in the absence of changes in body weight, body composition, or dietary habits suggests that exercise alone is effective in improving β-cell function. With regard to exercise intensity, it has been suggested that moderate-intensity exercise is actually slightly more effective than vigorous exercise in rescuing β-cell function (5), possibly because of an increased lipolytic activity associated with this intensity.
Exercise works in combination with insulin-sensitizing drugs to improve insulin sensitivity. In some cases, exercise can restore insulin sensitivity and eliminate the need for medication. In fact, some studies have shown that lifestyle interventions (exercise and diet) can be more effective than pharmaceutical therapy in preventing progression to T2D (9).
Another major goal of exercise in IR is to positively modify associated comorbidities. As mentioned earlier, IR is often compounded by additional metabolic abnormalities. Although nearly all associated comorbidities are positively modified through exercise, obesity is the most prevalent and thought to be a major determinant of IR (13,14). Often, it is advised for overweight and obese individuals with IR to lose 5–10% of body weight (1). However, subjects in a recent study experienced a 31% increase in insulin sensitivity after only a 3% reduction in body weight (12). Therefore, virtually any improvement in body weight and/or composition is likely to improve insulin sensitivity.
Insulin resistance is a complicated pathological condition. Although T2D remains a major health concern, exercise training provides a multifaceted approach to treating IR and potentially preventing progression to T2D. Exercise professionals should know the health concerns associated with IR and the mechanisms by which exercise improves IR. Additionally, it is important for exercise professionals to implement exercise strategies and educate clients to maximize health outcomes. The accompanying One-on-One article discusses specific exercise programming for persons with IR.
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