Sweet talk in the brain: Glucosensing, neural networks, and hypoglycemic counterregulation

Glucose is the primary fuel for the vast majority of cells, and animals have evolved essential cellular, autonomic, endocrine, and behavioral measures to counteract both hypo- and hyperglycemia. A central component of these counterregulatory mechanisms is the ability of specific sensory elements to detect changes in blood glucose and then use that information to produce appropriate counterregulatory responses. Here we focus on the organization of the neural systems that are engaged by glucosensing mechanisms when blood glucose concentrations fall to levels that pose a physiological threat. We employ a classic sensory–motor integrative schema to describe the peripheral, hindbrain, and hypothalamic components that make up counterregulatory mechanisms in the brain. We propose that models previously developed to describe how the forebrain modulates autonomic reflex loops in the hindbrain offer a reasoned framework for explaining how counterregulatory neural mechanisms in the hypothalamus and hindbrain are structured.