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Obesity is associated with peripheral insulin resistance in muscle, liver, and adipose tissue
INSULIN RESISTANCE OF THE CENTRAL NERVOUS SYSTEM:
RECORDING OF SPONTANEOUS ACTIVITY AND EVOKED
MAGNETIC FIELDS WITH MAGNETOENCEPHALOGRAPHY (MEG)
Katarina Porubska1, Dr. Hubert Preissl1, Dr. Andreas Fritsche2
1Institute of Medical Psychology and Behavioural Neurobiology, University of Tübingen,
2Department of Endocrinology, University Hospital Tübingen, Tübingen, Germany
Obesity is associated with peripheral insulin resistance in muscle, liver, and adipose tissue. Animal studies
suggest that the brain functions as an insulin-responsive organ and that central nervous insulin resistance induces
hyperphagia and obesity. We hypothesize that the human brain is also insulin-responsive and that in obese
subjects insulin effects are altered.
To investigate the role of central nervous effect of insulin we use whole-head magnetoencephalography (MEG)
during a 2-step hyperinsulinaemic clamp (versus saline) to
1) assess cortical insulin effects in humans and to
2) compare these effects between lean (N=10) and obese subjects (N=15).
All subjects are investigated on two different days, receiving intravenous three levels of insulin under constant
plasma glucose on one of the days, and placebo (saline) on the other day, in a simple-blind design. When a stable
state after the insulin (or placebo) infusion is reached, the magnetoencephalographic recordings of cortical
activity are performed. (fig.1)
In our first experimental design we recorded spontaneous cortical activity and evoked magnetic fields (auditory
mismatch negativity paradigm). We found significant effects in the theta band for spontaneous activity and in the
mismatch negativity (MMN) for the lean subjects. (fig. 2)
In lean subjects, the theta activity and MMN showed a significant enhancement during insulin administration
compared to the placebo condition. During the placebo experiment theta activity decreased from 375 ± 37 to 326
± 25 fT (p = 0.03) by the end of the second step. During the insulin experiment, in contrast, theta activity
increased from 347 ± 44 to 401 ± 40 fT (p < 0.001, ANOVA).
MMN remained unchanged during the placebo experiment. During the insulin experiment, MMN increased from
7.31 ± 0.08 to 7.37 ± 0.07 fT (p = 0.04, ANOVA) during the second step.
In overweight subjects the insulin effect on theta activity and MMN was absent.
In our second experimental design we record visual evoked magnetic fields. For the visual stimuli we chose a set
of pictures containing 64 food-relevant and 64 food-neutral photographs, which are visually presented to the
subjects in a randomized order. These two categories of visual stimuli do not differ in the ratings of arousal and
valence, but have significant different rating of potential to induce the feeling of hunger. Because obesity and
insulin resistance are associated with certain types of eating behavior, we aim to analyse whether the resulting
evoked magnetic fields differ between the two categories of stimuli (food-relevant vs. food-neutral), between the
groups of subjects (lean vs. overweight) and in the hyperinsulinaemic condition compared with placebo.
Our results from the first experimental design confirm the hypothesis that insulin modulates cerebrocortical
activity in healthy humans, which is absent in obese individuals. This suggests that cerebrocortical insulin
resistance is involved in human obesity and possibly in the pathogenesis of type 2 diabetes.
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