The role of ghrelin in the regulation of glucose homeostasis

Abstract

Ghrelin is a 28-amino acid (aa) stomach-derived peptide discovered in 1999 as the endogenous ligand for growth hormone secretagogue-receptor (GHS-R). Ghrelin-producing cells constitute a distinct group of endocrine cells dispersed throughout the gastric mucosa and to a lesser extent in the small intestine and the endocrine pancreas. Ghrelin plasma levels rise during fasting and chronic caloric restriction to stimulate food intake and fat storage and to prevent life-threatening falls in blood glucose. Plasma ghrelin levels decrease after a meal is consumed and in conditions of energy surplus (such as obesity). Ghrelin has emerged as a key player in the regulation of appetite and energy homeostasis. Ghrelin achieves these functions through binding the ghrelin receptor GHS-R in appetite-regulating neurons and in peripheral metabolic organs including the endocrine pancreas. Ghrelin levels are negatively correlated with body mass index (BMI) and insulin resistance. In addition, ghrelin secretion is impaired in obesity and insulin resistance. Several studies highlight an important role for ghrelin in glucose homeostasis. Genetic, immunological, and pharmacological blockade of ghrelin signaling resulted in improved glucose tolerance and insulin sensitivity. Furthermore, exogenous ghrelin administration was shown to decrease glucose-induced insulin release and increase glucose level in both humans and rodents. GHS-R was shown to be expressed in pancreatic β-cells and ghrelin suppressed insulin release via a Ca2+-mediated pathway. In this review, we provide a detailed summary of recent advances in the field that focuses on the role of insulin and insulin resistance in the regulation of ghrelin secretion and on the role of ghrelin in glucose-stimulated insulin secretion (GSIS).

Acylated and desacyl ghrelin are associated with hepatic lipogenesis, β-oxidation and autophagy: role in NAFLD amelioration after sleeve gastrectomy in obese rats

“…Thus, exogenous desacyl ghrelin administration acts as a potent insulin secretagogue, whereas acylated ghrelin decreases glucose-induced insulin release and increases glucose levels in both humans and rodents4445. In line with these observations, genetic, immunological, and pharmacological blockade of ghrelin signalling enhances glucose-stimulated insulin secretion and improves peripheral insulin sensitivity46. Thus, it seems plausible that ghrelin changes after sleeve gastrectomy also contribute, at least in part, to the observed improvement in insulin sensitivity after sleeve gastrectomy.…”

2D-DIGE as a strategy to identify serum biomarkers in Mexican patients with Type-2 diabetes with different body mass index

“…By contrary, ghrelin concentrations are negatively correlated with BMI in humans and insulin resistance29, the observed increased levels of leptin and decrease levels of ghrelin might be associated to the fat mass depots in obese groups(Table 1). Reports have indicated that insulin could induce leptin secretion and production event though body fat is the determinant factor of circulating leptin30.…”

Therapeutic Potential of Targeting the Ghrelin Pathway

“…Aside from hyperphagia and obesity, ghrelin is also extensively involved in the regulation of glucose metabolism [279]. Acyl ghrelin chiefly has hyperglycemic effects [280] and promotes insulin resistance [281,282], acting on both pancreatic islets to suppress insulin secretion [283] and on hepatocytes to stimulate glucose output [284], whereas des-acyl ghrelin may counteract the hyperglycemic effects of acyl ghrelin and enhance insulin sensitivity [282,284,285,286].…”