Hormonal signaling in the gut

Abstract

The gut is anatomically positioned to play a critical role in the regulation of metabolic homeostasis, providing negative feedback via nutrient sensing and local hormonal signaling. Gut hormones, such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), are released following a meal and act on local receptors to regulate glycemia via a neuronal gut-brain axis. Additionally, jejunal nutrient sensing and leptin action are demonstrated to suppress glucose production, and both are required for the rapid antidiabetic effect of duodenal jejunal bypass surgery. Strategies aimed at targeting local gut hormonal signaling pathways may prove to be efficacious therapeutic options to improve glucose control in diabetes.

Keywords: Bariatric Surgery; Diabetes; Fatty Acid; Food Intake; Glucose Metabolism; Hormones; Intestine.

FIGURE 1.

Gut peptide hormones and regulatory signals are released along the length of the gastrointestinal tract. Both ghrelin and leptin are secreted from the stomach, whereas CCK and GIP are secreted from I cells and K cells, respectively, in the duodenum. It is debated whether L cells, which secrete GLP-1, GLP-2, OXN, and PYY, are located in the duodenum. More distally secreted in the intestine are CCK and GIP from the jejunum, and GLP-1, GLP-2, OXN, and PYY from the ileum.

FIGURE 2.

Gut nutrient-sensing mechanisms and subsequent peptide hormone release in normal and DJB surgery settings. Nutrient influx in both the duodenum and the jejunum triggers hormonal release and downstream signaling to lower GP through a neuronal network. In the duodenum, these mechanisms are disrupted upon high fat feeding. DJB surgery results in the influx of nutrients and hormones, such as leptin, directly into the jejunum to suppress GP through downstream mechanisms. ACS, acyl-CoA synthetase; NTS, nucleus of the solitary tract; SGLT1, sodium glucose luminal transporter-1.