Impact of Hunger, Satiety, and Oral Glucose on the Association Between Insulin and Resting-State Human Brain Activity

To study the interplay of metabolic state (hungry vs. satiated) and glucose administration (including hormonal modulation) on brain function, resting-state functional magnetic resonance imaging (rs-fMRI) and blood samples were obtained in 24 healthy normal-weight men in a repeated measurement design. Participants were measured twice: once after a 36 h fast (except water) and once under satiation (three meals/day for 36 h). During each session, rs-fMRI and hormone concentrations were recorded before and after a 75 g oral dose of glucose. We calculated the amplitude map from blood-oxygen-level-dependent (BOLD) signals by using the fractional amplitude of low-frequency fluctuation (fALFF) approach for each volunteer per condition. Using multiple linear regression analysis (MLRA) the interdependence of brain activity, plasma insulin and blood glucose was investigated. We observed a modulatory impact of fasting state on intrinsic brain activity in the posterior cingulate cortex (PCC). Strikingly, differences in plasma insulin levels between hunger and satiety states after glucose administration at the time of the scan were negatively related to brain activity in the posterior insula and superior frontal gyrus (SFG), while plasma glucose levels were positively associated with activity changes in the fusiform gyrus. Furthermore, we could show that changes in plasma insulin enhanced the connectivity between the posterior insula and SFG. Our results indicate that hormonal signals like insulin alleviate an acute hemostatic energy deficit by modifying the homeostatic and frontal circuitry of the human brain.