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1 The Panum Institute, University of Copenhagen, Copenhagen Muscle Research Centre, Department of Medical Physiology, Copenhagen, Denmark
2 Rigshospitalet, Copenhagen Muscle Research Center, Department of Molecular Muscle Biology, Copenhagen, Denmark
* To whom correspondence should be addressed. E-mail: nilsh{at}mfi.ku.dk.
Insulin resistance is currently a major health problem. This may be because of a marked decrease in daily physical activity during the last decades combined with constant food abundance. This lifestyle collide with our genome, which was most likely selected in the late
Palaeolithic era (50.000 - 10.000 BC) by criteria that favoured survival in an environment that was characterized by fluctuations between periods of feast and famine. The theory of thrifty genes states that these fluctuations are required for an optimal metabolic function. We mimicked the fluctuations in 8 healthy young males (25.0±0.1 yrs (mean±SE); BMI: 25.7±0.4
kg . m-2) by subjecting them to intermittent fasting every second day for 20 h for 15 days. Euglycemic hyperinsulinemic (40 mU . min-1 . m-2) clamps were performed before and after
the intervention period. The subjects maintained body weight (86.4±2.3 kg; coefficient of
variation: 0.8±0.1%). Plasma FFA and 
-hydroxybutyrate concentrations were 347±18 µM
and 0.06±0.02 mM, respectively, after an overnight fast, but increased (p < 0.05) to 423±86
µM and 0.10±0.04 mM after 20 h fasting confirming that the subjects were fasting. Insulin
mediated whole body glucose uptake rates increased from 6.3±0.6 to 7.3±0.3 mg . kg-1 . min-1
(p=0.03) and the insulin-induced inhibition of adipose tissue lipolysis was more prominent after than before the intervention (p=0.05). After the 20 h fasting periods plasma adiponectin was increased compared to the basal levels before and after the intervention (5922±991 vs. 3860±784 ng . ml-1, p=0.02). This experiment is the first in humans to show that intermittent fasting increases insulin mediated glucose uptake rates and the findings are compatible with the thrifty gene concept.
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