From conditioned hypoglycemia to obesity: Following the data

While a graduate student in the late 1960s I trained rats to lower their blood glucose in response to an arbitrary cue, a phenomenon called conditioned hypoglycemia. Over many years as my colleagues and I attempted to understand the underlying physiology of conditioned insulin secretion and conditioned hypoglycemia, it became clear that there were many implications that were highly important, including the entry of insulin into the brain, the existence of insulin receptors in certain brain areas, neural reflexes that project to insulin-secreting B-cells in the pancreas, the entrainment of those reflexes to improve the efficiency of meal-taking, and the possibility of adiposity signals from the body to the brain that influence behavior and metabolism. This article summarizes how we tackled each of these areas of research.

► Describes the mechanisms underlying conditioning of hypoglycemia/insulin secretion
► Describes discoveries of blood–brain insulin transport and brain insulin receptors
► Describes entrainment of brain-islet reflexes to improve metabolic efficiency
► Describes insulin's role in communicating the level of body adiposity to the brain