Differential energetic response of brain vs. skeletal muscle upon glycemic variations in healthy humans

Abstract

The brain regulates all metabolic processes within the organism, and therefore, its energy supply is preserved even during fasting. However, the underlying mechanism is unknown. Here, it is shown, using (31)P-magnetic resonance spectroscopy that during short periods of hypoglycemia and hyperglycemia, the brain can rapidly increase its high-energy phosphate content, whereas there is no change in skeletal muscle. We investigated the key metabolites of high-energy phosphate metabolism as rapidly available energy stores by (31)P MRS in brain and skeletal muscle of 17 healthy men. Measurements were performed at baseline and during dextrose or insulin-induced hyperglycemia and hypoglycemia. During hyperglycemia, phosphocreatine (PCr) concentrations increased significantly in the brain (P = 0.013), while there was a similar trend in the hypopglycemic condition (P = 0.055). Skeletal muscle content remained constant in both conditions (P > 0.1). ANOVA analyses comparing changes from baseline to the respective glycemic plateau in brain (up to +15%) vs. muscle (up to -4%) revealed clear divergent effects in both conditions (P < 0.05). These effects were reflected by PCr/Pi ratio (P < 0.05). Total ATP concentrations revealed the observed divergency only during hyperglycemia (P = 0.018). These data suggest that the brain, in contrast to peripheral organs, can activate some specific mechanisms to modulate its energy status during variations in glucose supply. A disturbance of these mechanisms may have far-reaching implications for metabolic dysregulation associated with obesity or diabetes mellitus.

Brain size, body size and longevity

“…In this body-brain-energy balance, the denominator, 'brain metabolism' (Y), adequately fulfils the criteria for reference variables, as cerebral morphological and energetic changes are known to be very small even under conditions of long-term or short-term energy depletion. 15,16 Every individual subject appears to strive for an optimal allocation of energy resources between the brain and the periphery in order to realize its best adaptive capacity. Considering this background, the following two questions are posed here: (1) is the relationship between body and brain energy metabolism somehow linked to longevity in humans?, and (2) if so, can we integrate such a finding into the laws of body-brain allometry that are already well established over a wider range of body sizes ranging in size from the goldfish to the elephant?…”

Deductive Functional Assignment of Elements in Appetite Regulation

“…This selection has been supported by the discussion of the underlying physiological mechanisms and by the ability of the selected models to explain the experimental observations [14,15]. Furthermore, the model has been adapted to different exogenic conditions like social and natural cycling.…”

“…The deductive approach determines the necessity of appetite generation depending on the brain energy level in contrast to the glucostatic theory [13], which cannot explain the old observation of nearly constant brain energy level during atrophic phases [14] nor new experimental results of the constant brain energy under cyclic intake and need [15], cf. Section 5.…”

Zentrale Glukoseregulation

“…Die Befunde von Marie Krieger lassen sich nur dann erklä-ren, wenn eine starke Gehirn-Pull-Komponente vorliegt, die Energie bedarfsgemäß für das Gehirn Zwischen dem Gehirn und den anderen Organen besteht eine Art Konkurrenzsituation um Energieressourcen CME aus dem Körper anfordert. Die Priorität des Gehirns wird nicht nur im chronischen Prozess der Abmagerung sichtbar, sondern auch in akuten Belastungen des Glukosestoffwechsels wie bei akuter Hypo-oder Hyperglykämie [19]. Das Gehirn behandelt die Regulation seines eigenen Energiegehaltes vorrangig.…”