The cerebrocortical response to hyperinsulinemia is reduced in overweight humans: a magnetoencephalographic study.
Animal studies have shown that the brain is an insulin-responsive organ and that central nervous insulin resistance induces obesity and disturbances in glucose metabolism. In humans, insulin effects in the brain are poorly characterized. We used a magnetoencephalography approach during a two-step hyperinsulinemic euglycemic clamp to (i) assess cerebrocortical insulin effects in humans, (ii) compare these effects between 10 lean and 15 obese subjects, and (iii) test whether the insulin receptor substrate (IRS)-1 Gly972Arg polymorphism in the insulin-signaling cascade modifies these effects. Both spontaneous and stimulated (mismatch negativity) cortical activity were assessed. In lean humans, stimulated cortical activity (P = 0.046) and the beta and theta band of spontaneous cortical activity (P = 0.01 and 0.04) increased with insulin infusion relative to saline. In obese humans, these effects were suppressed. Moreover, the insulin effect on spontaneous cortical activity correlated negatively with body mass index and percent body fat (all r < -0.4; all P < 0.05) and positively with insulin sensitivity of glucose disposal (theta band, r = 0.48, P = 0.017). Furthermore, insulin increased spontaneous cortical activity (beta band) in carriers of wild-type IRS-1, whereas, in carriers of the 972Arg allele, this insulin effect was absent (P = 0.01). We conclude that, in lean humans, insulin modulates cerebrocortical activity, and that these effects are diminished in obese individuals. Moreover, cerebrocortical insulin resistance is found in individuals with the Gly972Arg polymorphism in IRS-1, which is considered a type 2 diabetes risk gene.
Tschritter
Otto
O
Medizinische Klinik der Universität, University of Tübingen, 72076 Tübingen, Germany.
Preissl
Hubert
H
Hennige
Anita M
AM
Stumvoll
Michael
M
Porubska
Katarina
K
Frost
Rebekka
R
Marx
Hannah
H
Klösel
Benjamin
B
Lutzenberger
Werner
W
Birbaumer
Niels
N
Häring
Hans-Ulrich
HU
Fritsche
Andreas
A
D000328:Adult; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000473:pathology*; D007328:Insulin / Q000378:metabolism; D015225:Magnetoencephalography / Q000379:methods*; D008297:Male; D009765:Obesity; D050177:Overweight; D011110:Polymorphism, Genetic
D007328:Insulin; D005947:Glucose