The Gastrointestinal Tract as an Integrator of Mechanical and Hormonal Response to Nutrient Ingestion

Abstract

Glucose tolerance after meal ingestion in vivo is the result of multiple processes that occur in parallel. Insulin secretion together with reciprocal inhibition of glucagon secretion contributes to glucose tolerance. However, other factors beyond glucose effectiveness and insulin action require consideration. The absorption of ingested nutrients and their subsequent systemic rate of appearance largely depend on the rate of delivery of nutrients to the proximal small intestine. This is determined by the integrated response of the upper gastrointestinal tract to a meal. While gastric emptying is probably the most significant component, other factors need to be considered. This review will examine all processes that could potentially alter the fraction and rate of appearance of ingested nutrients in the peripheral circulation. Several of these processes may be potential therapeutic targets for the prevention and treatment of diabetes. Indeed, there is increased interest in gastrointestinal contributions to nutritional homeostasis, as demonstrated by the advent of antidiabetes therapies that alter gastrointestinal motility, the effect of bariatric surgery on diabetes remission, and the potential of the intestinal microbiome as a modulator of human metabolism. The overall goal of this review is to examine current knowledge of the gastrointestinal contributions to metabolic control.

Figure 1

GLP-1 increases gastric fasting and postprandial volume. However, in the presence of cardiovagal dysfunction, GLP-1 does not alter fasting or postprandial gastric volume. Reprinted with permission from Delgado-Aros et al. Effects of glucagon-like peptide-1 and feeding on gastric volumes in diabetes mellitus with cardio-vagal dysfunction. Neurogastroenterol Motil 2003;15:435–443.

Figure 2

Interaction of nutrient intake and neurohormonal responses. AAs, amino acids; CHO, carbohydrates. Reprinted with permission from Camilleri. Peripheral mechanisms in appetite regulation. Gastroenterology 2015;148:1219–1233.

Figure 3

Patterns of gastric emptying of liquids and solids in health and in gastroparesis (reprinted with permission from Camilleri and Shin [59]).