US adults take between approximately 2,000 and approximately 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 (VO2 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 pAktthr308/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 VO2 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.