Free fatty acids (FFAs) are not only nutrients, but also act as regulators of various physiological functions. Free fatty acid receptors (FFARs), expressed on enteroendocrine cells (EECs) in the intestinal tract, are involved in the secretion of various enteroendocrine hormones stimulated by ingestion of dietary fat consisting primarily of long-chain fatty acids (LCFAs) and short-chain fatty acids (SCFAs) produced by the intestinal microflora. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are enteroendocrine hormones secreted from the EECs in response to nutrient intake, promoting insulin secretion from pancreatic beta-cells, and referred to collectively as incretins. FFAR1 and FFAR4, which are long-chain fatty acid receptors, and FFAR2 and FFAR3, known as short-chain fatty acid receptors, are reportedly involved in the mechanism of incretin secretion. Incretins have multifaceted bioactivities favoring blood glucose normalization and inhibition of weight gain, and FFARs may be potential drug targets for type 2 diabetes and obesity. This review outlines the role of FFARs in the mechanism of incretin secretion.

Blood glucose homeostasis is maintained by appropriate insulin secretion and signaling in response to blood glucose elevations caused by ingesting food. The ability to secrete insulin is generally lower in East Asian people, and maintaining the insulin secretory function of pancreatic β-cells is therefore essential for preventing type 2 diabetes in this population. The two intestinal incretin hormones, gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP-1), act directly or indirectly on pancreatic β-cells to promote cell proliferation, inhibit cell death, and amplify glucose-stimulated insulin secretion. The use of incretin to maintain blood glucose homeostasis and prevent diabetes is a promising pharmacological strategy that would be achievable using functional foods. This article summarizes the role of insulin and incretin hormones on type 2 diabetes, and highlights functional foods that promote incretin secretion or mimic its actions, and could therefore contribute to diabetes disease management or prevention.

The gastrointestinal tract acts as an interface between the external and internal milieux of the body. Among a variety of cells in the gastrointestinal tract, enteroendocrine cells are known to receive molecular information from the lumen, also from outside the body, secrete gastrointestinal hormones to the inside of the body, and transmit food information to the body. For example, proteins are fragmented by gastrointestinal enzymes with different substrate specificities, generating a vast number of molecular species. Enzymatic digests, which were previously made up of unidentified molecules, can now be detected and annotated comprehensively. Furthermore, many bioactive molecules produced by enzymatic digestion have been discovered, and the structural rules necessary for their bioactivity have been clarified. This has led to the identification of exogenous signals derived from food at the molecular level and a marked increase in the resolution of interactions with the gastrointestinal tract. In this review, we focus on exogenous peptides, including food-derived peptides, and provide an overview of their regulation of gastrointestinal hormone signaling. In addition, we present examples of peptides with diverse molecular structures and bioactivities that have become excellent probes for revealing new food signaling pathways and age-related alterations.