Insulin Pathway Takes a Jog: Workouts might benefit young and old by employing different molecular messengers (Insulin signaling)
Authors: Miller Katharine 
Published: August 2003

Athletes of all ages can handle a sugar-laced Hershey bar better than their couch potato counterparts can. That's because workouts boost muscle cells' ability to respond to insulin, the hormone that instructs such cells to bring glucose aboard. Hitting the gym provides protection from the root cause of type II diabetes: insulin resistance, a condition in which muscle cells lose the ability to take up glucose efficiently even when insulin is present. But a new study suggests that hours spent riding a stationary bike might trigger different molecular tripwires in young and old people. The work highlights the importance of studying insulin resistance in older subjects.

When insulin binds to a receptor attached to the exterior of a muscle cell, it sets off a sequence of events within. First it recruits several insulin receptor substrates (IRSs). IRS-1 then docks with and activates many other molecules, including phosphatidylinositol (PI) 3-kinase, which incites poorly defined cellular pathways that relay insulin's signal. As a result of this signaling cascade, the insulin-sensitive glucose transporter GLUT-4 moves to the muscle cell membrane, where it helps sugar flow into the cell. Scientists know little about how exercise affects the many molecular couriers that handle insulin's message before it reaches GLUT-4. Understanding the influence of exercise on these envoys might help pinpoint targets for drugs that can reverse or prevent insulin resistance, as workouts do. Finding such drug targets matters most to older people: After age 30, sedentary humans' resistance to insulin increases, rendering them vulnerable to high cholesterol levels, arterial damage, cardiac problems, hyperglycemia, obesity, and type II diabetes.

To identify molecular messengers whose activity might change in response to exercise, Tanner and colleagues first examined the muscle tissue of otherwise sedentary young (19- to 28-year-old) men before and after a weeklong endurance exercise regimen. In that study, published a year ago, the subjects exhibited not only an enhanced response to insulin but also increased PI 3-kinase activity. Expecting the same result, the researchers placed nine inactive 50- to 70-year-old men on the same regimen and followed the same experimental protocol. Like in the young men, sugar in the older subjects' blood moved into cells more efficiently after the week's exercise than it had before the workouts. But, unlike the muscle cells of young men, those of older men showed little change in PI 3-kinase activity after the exercise program.

Older men still experience the increased insulin sensitivity that comes with short-term exercise, but the new results suggest that they don't achieve it by boosting PI 3-kinase activity as young men do. Exercise might benefit the older men either by altering a molecular messenger in the murky realm downstream of PI 3-kinase or by exploiting a signaling pathway that doesn't involve PI 3-kinase. Further study of more people at more time points and over a longer course of exercise is required to confirm the findings. But the results introduce a new possibility for how exercise impacts insulin signaling with age. Understanding the disparity between young and old people's responses to exercise might help scientists develop additional ways to maintain insulin sensitivity in older adults.

--Katharine Miller; suggested by James M. Harper

C. J. Tanner, T. R. Koves, R. L. Cortright, W. J. Pories, Y.-B. Kim, B. B. Kahn, G. L. Dohm, J. A. Houmard, Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in middle-aged men.
Am. J. Physiol. Endocrinol. Metab.
282
, E147-E153 (2002).
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