The data summarized above highlight the complexity of nutrient and hormone sensing and the prominent role of the hypothalamus as an integrative center. Subpopulations of neurons, particularly in the hypothalamus, are selectively either activated or inhibited by nutrients. While interaction of nutrients with specific receptors modulates activity of a specific population of neurons, some of the signaling effects of nutrients appear to be dependent on intracellular metabolism, production of ATP, and the subsequent activation of the KATP channel. As an example, neurons need to integrate signals from glucose and fatty acid metabolism as well as metabolic signals from surrounding cells such as astrocytes. Thus, these neurons are ideally suited to respond differentially under a variety of metabolic conditions. These complex crosstalk mechanisms should provide clues to an understanding of the relationship between brain sensing and metabolic diseases such as type 2 diabetes. Data presented here also point out the crucial role of gut-brain interaction in nutrient and hormone sensing and regulation of energy homeostasis. Particularly, the portal vein, which receives the primary information of nutrients and gastrointestinal hormones, is a strategic point of indirect metabolic sensing by the brain. Interestingly, nutrient sensing in the portal vein requires the induction of intestinal gluconeogenesis through a reflex arc, allowing the nutrients to extend the duration of their signal to the brain after digestion, during the post-absorptive state. Finally, the brain translates sensory information to control energy homeostasis and more particularly insulin secretion, via the autonomic nervous system. The modulation of the autonomic nervous system by brain glucose sensing is crucial for the counter-regulatory responses induced by hypoglycemia and for the proliferation of β-cells in the postnatal period. In addition, this system is required for the fine tuning of insulin secretion, including the regulation of insulin secretion pulsatility and the potentiation mechanisms of insulin release.
“Neural Orchestration of Metabolism and Islet function”
I. General points on the central control of energy balance and food intake
II. Mechanisms of direct detection of nutrients and hormones by the brain
III. Gastrointestinal and vagal detection of nutrients
IV. Control of β-cell function by the brain
Lectures during IGIS meeting