Glucose‐dependent insulinotropic polypeptide secretion after oral macronutrient ingestion: The human literature revisited and a systematic study in model experiments in mice

AIMS/INTRODUCTION: The incretin hormone glucose‐dependent insulinotropic polypeptide (GIP) is secreted after meal ingestion. This study explored the relative influence of classes of macronutrients on GIP secretion. MATERIALS AND METHODS: The human literature was revisited by identifying articles from PubMed using key words GIP, macronutrients, carbohydrates, fat, protein, healthy subjects. In model experiments in anesthetized mice, glucose (25–125 mg), protein (15–120 mg), fat emulsion (6–100 mg) or saline was given orally with determination of GIP levels. RESULTS: The literature survey identified 15 studies in which glucose, protein or fat was administered to healthy subjects. All three classes of macronutrients stimulated GIP secretion with a 30–45 min peak after glucose and protein, and a more prolonged release after fat. Limitations in study designs preclude firm conclusions on the relative potency of the macronutrients. In mice, glucose was more potent to stimulate GIP secretion than fat and protein, with no significant difference between protein and fat. By co‐administration of the macronutrients at moderate caloric combinations, a synergistic stimulation of GIP secretion was observed. In contrast, when raising the glucose challenge together with protein and fat, no synergy, but an additive effect, was evident. CONCLUSIONS: Glucose, protein and fat all stimulate GIP secretion in humans and mice. In mice, glucose is more potent than fat and protein, and there is also a synergy between the macronutrients on GIP secretion at moderate caloric doses. Further studies are warranted in humans to explore the relative potency of macronutrients.