A 2-wk reduction of ambulatory activity attenuates peripheral insulin sensitivity

Krogh-Madsen R, Thyfault JP, Broholm C, Mortensen OH, Olsen RH, Mounier R, Plomgaard P, van Hall G, Booth FW, Pedersen BK. A 2-wk reduction of ambulatory activity attenuates peripheral insulin sensitivity. J Appl Physiol 108: 1034-1040, 2010. First published December 31, 2009; doi:10.1152/japplphysiol.00977.2009.-US adults take between similar to 2,000 and similar to 12,000 steps per day, a wide range of ambulatory activity that at the low range could increase risk for developing chronic metabolic diseases. Dramatic reductions in physical activity induce insulin resistance; however, it is uncertain if and how low ambulatory activity would influence peripheral insulin sensitivity. We aimed to explore if healthy, nonexercising subjects who went from a normal to a low level of ambulatory activity for 2 wk would display metabolic alterations including reduced peripheral insulin sensitivity. To do this, ten healthy young men decreased their daily activity level from a mean of 10,501 +/- 808 to 1,344 +/- 33 steps/day for 2 wk. Hyperinsulinemic-euglycemic clamps with stable isotopes and muscle biopsies, maximal oxygen consumption ((V) over dotO(2) max) tests, and blood samples were performed pre- and postintervention. A reduced number of daily steps induced a significant reduction of 17% in the glucose infusion rate (GIR) during the clamp. This reduction was due to a decline in peripheral insulin sensitivity with no effect on hepatic endogenous glucose production. The insulin-stimulated ratio of pAkt(thr308)/total Akt decreased after step reduction, with a post hoc analysis revealing the most pronounced effect after 4 h of insulin infusion. In addition, the 2-wk period induced a 7% decline in (V) over dotO(2) max (ml/min; cardiovascular fitness). Lean mass of legs, but not arms and trunk, decreased concurrently. Taken together, one possible biological cause for the public health problem of Type 2 diabetes has been identified. Reduced ambulatory activity for 2 wk in healthy, nonexercising young men significantly reduced peripheral insulin sensitivity, cardiovascular fitness, and lean leg mass.