Cephalic phase insulin release: A review of its mechanistic basis and variability in humans

Cephalic phase insulin release (CPIR) is a transient pulse of insulin that occurs within minutes of stimulation from foods or food-related stimuli. Despite decades of research on CPIR in humans, the body of literature surrounding this phenomenon is controversial due in part to contradictory findings . This has slowed progress towards understanding the sensory and neural basis of CPIR, as well as its overall relevance to health. This review examines up-to-date knowledge in CPIR research and identifies sources of CPIR variability in humans in an effort to guide future research. The review starts by defining CPIR and discussing its presumed functional roles in glucose homeostasis and feeding behavior. Next, the types of stimuli that have been reported to elicit CPIR, as well as the sensory and neural mechanisms underlying the response in rodents and humans are discussed, and areas where knowledge is limited are identified. Finally, factors that may contribute to the observed variability of CPIR in humans are examined, including experimental design, test procedure, and individual characteristics. Overall, oral stimulation appears to be important for eliciting CPIR, especially when combined with other sensory modalities (vision, olfaction, somatosensation). While differences in experimental design and testing procedure likely explain some of the observed inter- and intra-study variability, individual differences also appear to play an important role. Understanding sources of these individual differences in CPIR will be key for establishing its health relevance.