The delivery of nutrients from the stomach into the duodenum and their subsequent interaction with the small intestine to stimulate incretin hormone release are central determinants of the glycemic response. The incretin effect has hitherto been attributed to the secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) from enteroendocrine cells in the intestinal epithelium. A number of recent studies have yielded fundamental insights into the influence of individual nutrients on incretin release and the mechanisms involved in the detection of carbohydrates, fats, and proteins by enteroendocrine cells, including the K(ATP) channel, sodium-glucose cotransporter 1 (SGLT1), sweet taste receptors, G-protein-coupled receptors (GPRs), and oligopeptide transporter 1 (PepT1). Dietary modification, including modifying macronutrient composition or the consumption of "preloads" in advance of a meal, represents a novel approach to manipulate the incretin response and thereby regulate glucose homeostasis in patients with type 2 diabetes. This review focuses on the effects of individual nutrients on incretin hormone secretion, our current understanding of the signaling mechanisms that trigger secretion by enteroendocrine cells, and the therapeutic implications of these observations.
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