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Centre of Inflammation and Metabolism (CIM)


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145Muscle-to-fat interaction: a two-way street?
Pedersen BK
J Physiol 2010; 588(Pt 1): 21
PubMed ID: 20045903

US adults take between ~2,000 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, non-exercising subjects who went from a normal to a low level of ambulatory activity for two weeks 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 weeks. Hyperinsulinemic-euglycemic clamps with stable isotopes and muscle biopsies, maximal oxygen consumption (VO2max) tests, and blood samples were performed pre and post intervention.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 two-week period induced a 7% decline in VO2max (ml/min; cardiovascular fitness). Lean mass of legs, but not arms and truck, decreased concurrently. Taken together, one possible biological cause for the public health problem of type 2 diabetes has been identified. Reduced ambulatory activity for two weeks in healthy, non-exercising young men significantly reduced peripheral insulin sensitivity, cardiovascular fitness, and lean leg mass. Key words: Inactivity, Insulin resistance, Clamp, Insulin signalling.

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