Proximal Disruption of Brain Energy Supply Raises Systemic Blood Glucose: A Systematic Review

This work joins a series that methodically tests the predictions of the Selfish-Brain theory. The theory postulates a vital ability of the mammalian brain, namely to give priority to its own energy metabolism. The brain behaves "selfishly" in this respect. For the cerebral artery occlusion studied here, the theory predicts an increase in blood glucose concentration, what becomes the hypothesis to be tested. We conducted a systematic review of cerebral-artery-occlusion papers to test whether or not the included studies could confirm this hypothesis. We identified 239 records, screened 231 works by title or abstract, and analyzed 89 by full text. According to strict selection criteria (set out in our PROSPERO preregistration, complying with PRISMA guidelines), 7 papers provided enough information to decide on the hypothesis. Our hypothesis could be fully confirmed for the 3 to 24 h after the onset of a transient 2 h or permanent occlusion. As for the mechanism, the theory predicts that the energy-deprived brain suppresses insulin secretion via the sympathoadrenal system, thereby preventing insulin-mediated glucose uptake into muscle and fat and, as a result, enhancing insulin-independent glucose uptake via the blood-brain barrier. Evidence from our included studies actually demonstrated cerebral insulin suppression. In all, the current work confirms the second major prediction of the Selfish-Brain theory that relates to a proximal bottleneck of the cerebral supply chain, cerebral artery occlusion. Its first major prediction relates to a distal supply bottleneck, caloric restriction, and is fulfilled as shown by our previous work, whereas the prediction of the long held gluco-lipostatic theory, which sees the brain as only passively supplied, is violated (Sprengell et al., 2021). The crucial point was that caloric restriction elicits smaller changes in mass (energy) in the brain than in the body. Taken together, the evidence from the current and previous work clearly shows that the most accurate predictions are possible with a theory that views the brain as an independently self-regulating energy compartment occupying a primary position in energy metabolism.