Gut Hormones in Glucose Homeostasis and Current Treatment Approach in the Control of T2DM: A Succinct Review

Abstract

Gut–brain axis plays a key role in the regulation of energy homeostasis and glucose metabolism through various hormones. Gut hormones are peptides synthesized by specialized cells of enteroendocrine located in the epithelium of the stomach, small bowel and large bowel. Gut hormones activate neural circuits to signal peripheral organs for coordination of overall energy intake and assimilation. Incretins, Leptin, CCK, Oxyntomodulin, PYY and Gastrin are the major gut hormones involved in glucose metabolism. Group of gut peptides that are secreted after nutrient intake and stimulate insulin secretion together with hyperglycaemia are known as incretin hormones. Certain gut hormones like cholecystokinin (CCK) and gastrin are reported to activate pathways that promote islet neogenesis and improve glucose homeostasis in type 2 diabetes mellitus (T2DM). Currently DPP-4 resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of DPP-4 activity (incretin enhancers) are being successfully used clinically for treatment of T2diabetes mellitus. Presently, hormonal synergy is of therapeutic interest for treatment of diabetes mellitus. Augmenting the biological activity of the “incretin” hormones to address many of the pathophysiological problems of diabetes is an effort in this direction. Gut hormones such as OXM, ghrelin and PYY play crucial role in the regulation of glucose. Pleirotropic actions of leptin reported to lower glucose is also, an area of investigation for hyperglycemia. Studies have proved that these hormonal actions are a possible platform for therapeutic development in T2DM management.