Nutritional regulation of glucagon-like peptide-1 secretion

Abstract

Glucagon-like peptide-1 (GLP-1), released from L-cells in the intestinal epithelium, plays an important role in postprandial glucose homeostasis and appetite control. Following the recent therapeutic successes of antidiabetic drugs aimed at either mimicking GLP-1 or preventing its degradation, attention is now turning towards the L-cell, and addressing whether it would be both possible and beneficial to stimulate the endogenous release of GLP-1 in vivo. Understanding the mechanisms underlying GLP-1 release from L-cells is key to this type of approach, and the use of cell line models has led to the identification of a variety of pathways that may underlie the physiological responses of L-cells to food ingestion. This review focuses on our current understanding of the signalling mechanisms that underlie L-cell nutrient responsiveness.

Figure 1. A working model for nutrient-stimulated GLP-1 release

Upper panel: enteroendocrine cells in the intestinal epithelium (grey) detect nutrients passing in the lumen, but also respond to paracrine, neural and hormonal stimuli. Lower panel: potential nutrient-sensing pathways in an individual L-cell include electrogenic uptake pathways, such as SGLT1, metabolic closure of K_ATP channels and activation of G protein-coupled receptors (GPCRs). Downstream signalling pathways include elevated cAMP and [Ca²⁺], which stimulate vesicle fusion and the consequent release of GLP-1.