Le Magnen described this first wave of insulin as increasing “the metabolic background of hunger.” In other words, this wave of insulin shuts down the mobilization of fat from the adipose tissue and stores away blood glucose in preparation for the imminent arrival of more. This leaves the circulation relatively depleted of nutrients. As a result, hunger increases. And this makes the food seem to taste even better. “In man,” suggested Le Magnen, “it is reflected by the increased feeling of hunger at the beginning of a meal expressed in the popular adage in French: L’appétit vient en mangeant”—i.e., “the appetite comes while eating.” As the meal continues and our appetite is satisfied, the metabolic background of hunger ebbs with the flood of nutrients into the circulation, and so the perceived palatability of the food wanes as well. Palatability, by this logic, is a learned response, conditioned largely by hunger, which in turn is a response to the pattern of insulin secretion and the availability of fatty acids and/or glucose in the circulation.

A related observation that has been a part of scientific study since Pavlov’s famous research in the nineteenth century is that the smell, sight, or even thought of food will induce a cascade of physiological reactions. These include the secretion of saliva, gastric juices, and, not surprisingly, insulin. By the 1970s, these cephalic*136 reflexes had been studied in humans, rats, monkeys, cats, sheep, and rabbits. Le Magnen’s student Stylianos Nicolaidis had demonstrated that rats will secrete insulin in response to the mere taste of a sweet substance, and it doesn’t matter whether it is sugar or a no-calorie sugar substitute. The perceived taste of sweetness is sufficient to stimulate insulin secretion. Just as Pavlov demonstrated that dogs will salivate at the sound of a bell they have learned to associate with feeding, Stephen Woods and his colleagues demonstrated that rats will secrete insulin when confronted with similar eating-related stimuli. (These researchers arbitrarily chose the smell of mentholatum, a mixture of menthol and petroleum jelly, more commonly used as a topical rub for chest colds.) Humans will do the same. This reflexive release of insulin, Nicolaidis suggested, is “pre-adaptive”: it anticipates the effects of a meal or a particular food, and so prepares the body. As Mark Friedman describes it, this cephalic release of insulin also serves to clear the circulation of “essentially anything an animal or a person can use for fuel. Not just blood sugar, but fatty acids, as well. All those nutrients just go away.” Hence, the thought of eating makes us hungry, because the insulin secreted in response depletes the bloodstream of the fuel that the peripheral tissues and organs need to survive.