Using the lymphatics to study nutrient absorption and the secretion of gastrointestinal hormones

Abstract

The lymph fistula rat model has traditionally been used to study the intestinal absorption of nutrients, especially lipids, but recently this model has also been used for studying the secretion of incretin hormones by the small intestine. The small intestine is not only responsible for the digestion and transport of dietary triacylglycerol, through the formation of chylomicrons, but it also secretes the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) from enteroendocrine cells. Ultimately, both chylomicrons and incretins are found in lymph. Advantages of the lymph fistula rat model in studying chylomicron and incretin secretion are numerous and include: 1) the concentrations of incretin hormones are higher in lymph than in peripheral or portal plasma; 2) there is reduced degradation of incretin hormones by DPP-IV in the lymph compartment; 3) less dilution by the circulating fluid; 4) this model allows the continuous collection of lymph from conscious animals, eliminating any potential side effects on lymph flow and gastrointestinal function due to anesthesia; and finally, and perhaps most importantly, and 5) the concentration in the intestinal lymph provides a physiologically accurate representation of the hormonal milieu within the intestinal mucosa where incretins may interact with enteroendocrine and/or dendritic cells and signal through the enteric or autonomic neurons. The importance of GIP and GLP-1 in health and disease is becoming more apparent, especially as the prevalence of type 2 diabetes and other metabolic disorders increases. This review focuses on the use of the lymph fistula rat as a model to study the secretion of incretins, as well as dietary lipid.