Cerebrocortical beta activity in overweight humans responds to insulin detemir.

Abstract

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.

METHODOLOGY/PRINCIPAL FINDINGS:

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/SIGNIFICANCE:

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.

• Authors: Otto Tschritter, Anita M Hennige, Hubert Preissl, Katarina Porubska, Silke A Schäfer, Werner Lutzenberger, Fausto Machicao, Niels Birbaumer, Andreas Fritsche, Hans-Ulrich Häring
• Journal: PloS one (PLoS One) Vol. 2 Issue 11 Pg. e1196 (Nov 21 2007) ISSN: 1932-6203 [Electronic] United States
• PMID: 18030331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Insulin, Long-Acting
• Insulin Detemir

Topics

• Adult
• Case-Control Studies
• Cerebral Cortex (drug effects, physiopathology)
• Female
• Humans
• Insulin (analogs & derivatives, pharmacology, therapeutic use)
• Insulin Detemir
• Insulin, Long-Acting
• Male
• Overweight (physiopathology)