In Vivo Models for Incretin Research: From the Intestine to the Whole Body

Abstract

Incretin hormones are produced by enteroendocrine cells (EECs) in the intestine in response to ingested nutrient stimuli. The incretin effect is defined as the difference in the insulin secretory response between the oral glucose tolerance test and an isoglycemic intravenous glucose infusion study. The pathophysiology of the decreased incretin effect has been studied as decreased incretin sensitivity and/or β-cell dysfunction per se. Interestingly, robust increases in endogenous incretin secretion have been observed in many types of metabolic/bariatric surgery. Therefore, metabolic/bariatric surgery has been extensively studied for incretin physiology, not only the hormones themselves but also alterations in EECs distribution and genetic expression levels of gut hormones. These efforts have given us an enormous understanding of incretin biology from synthesis to in vivo behavior. Further innovative studies are needed to determine the mechanisms and targets of incretin hormones.

Keywords: Bariatric surgery; Enteroendocrine cells; Incretins.

Fig. 1. Intravenous glucose infusion rates during an isoglycemic intravenous glucose infusion (IIGI) study in subjects with (A) normal glucose tolerance (NGT) or (B) type 2 diabetes mellitus (T2DM). Plasma glucose profiles of oral glucose tolerance test (OGTTs) (filled symbol) and IIGI studies (open symbol) in subjects with (C) NGT or (D) T2DM. Adapted from Oh et al. [21], with permission from John Wiley and Sons.