Ghrelin regulation of glucose metabolism

Abstract

Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), are implicated in the regulation of glucose metabolism via direct actions in the pancreatic islet, as well as peripheral insulin-sensitive tissues and the brain. Although many studies have explored the role of ghrelin in glucose tolerance and insulin secretion, a complete mechanistic understanding remains to be clarified. This review highlights the local expression and function of ghrelin and GHSR1a in pancreatic islets and how this axis may modulate insulin secretion from pancreatic β-cells. Additionally, we discuss the effect of ghrelin on in vivo glucose metabolism in rodents and humans, as well as the metabolic circumstances under which the action of ghrelin may predominate.

Keywords: ghrelin; glucose tolerance; insulin; insulin secretion.

Figure 1:

Summary of ghrelin actions on glucose homeostasis. From top, clockwise: In the brain, ghrelin action in the brain increases growth hormone (GH) and Adrenocorticotropic hormone (ACTH) secretion and sympathetic nervous system (SNS) output and enhances food seeking and food reward; in the adrenal glands, ghrelin increases epinephrine and cortisol; in adipose tissue, ghrelin increases lipolysis; in the stomach, ghrelin increases gastric emptying; in the liver, ghrelin has been reported to increase, or not effect, hepatic glucose production; in muscle, ghrelin decreases glucose uptake; in the pancreas, ghrelin increases somatostatin and decreases insulin and glucagon secretion. The actions of ghrelin on these tissues have systemic effects to reduce pancreatic β-cell function, reduce insulin action, and restore glycemia.