Cerebrocortical beta activity in overweight humans responds to insulin detemir.
BACKGROUND
Insulin stimulates cerebrocortical beta and theta activity in lean humans. This effect is reduced in obese individuals indicating cerebrocortical insulin resistance. In the present study we tested whether insulin detemir is a suitable tool to restore the cerebral insulin response in overweight humans. This approach is based on studies in mice where we could recently demonstrate increased brain tissue concentrations of insulin and increased insulin signaling in the hypothalamus and cerebral cortex following peripheral injection of insulin detemir.


RESULTS
We studied activity of the cerebral cortex using magnetoencephalography in 12 lean and 34 overweight non-diabetic humans during a 2-step hyperinsulinemic euglycemic clamp (each step 90 min) with human insulin (HI) and saline infusion (S). In 10 overweight subjects we additionally performed the euglycemic clamp with insulin detemir (D). While human insulin administration did not change cerebrocortical activity relative to saline (p = 0.90) in overweight subjects, beta activity increased during D administration (basal 59+/-3 fT, 1(st) step 62+/-3 fT, 2(nd) step 66+/-5, p = 0.001, D vs. HI). As under this condition glucose infusion rates were lower with D than with HI (p = 0.003), it can be excluded that the cerebral effect is the consequence of a systemic effect. The total effect of insulin detemir on beta activity was not different from the human insulin effect in lean subjects (p = 0.78).


CONCLUSIONS
Despite cerebrocortical resistance to human insulin, insulin detemir increased beta activity in overweight human subjects similarly as human insulin in lean subjects. These data suggest that the decreased cerebral beta activity response in overweight subjects can be restored by insulin detemir.
Tschritter
Otto
O
Department of Internal Medicine IV, University of Tübingen, Tübingen, Germany.
Hennige
Anita M
AM
Preissl
Hubert
H
Porubska
Katarina
K
Schäfer
Silke A
SA
Lutzenberger
Werner
W
Machicao
Fausto
F
Birbaumer
Niels
N
Fritsche
Andreas
A
Häring
Hans-Ulrich
HU
D000328:Adult; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting; D008297:Male; D050177:Overweight / Q000503:physiopathology*
D007328:Insulin; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir