Abstract
Ghrelin is a 28-amino-acid peptide that displays a strong growth hormone- (GH-) releasing activity through the activation of the growth hormone secretagogue receptor (GHSR). The first studies about role of ghrelin were focused on its orexigenic ability, but despite indisputable pharmacological data, the evidence for a physiological role for ghrelin in the control of appetite is much less clear. Mice with targeted deletion of either ghrelin or the GHSR exhibit an essentially normal metabolic phenotype when fed a regular chow diet, suggesting that ghrelin may have a redundant role in the regulation of food intake. RNAs for ghrelin as well as GHSR are expressed in the pancreas of rats and humans and several studies propose that ghrelin could have an important function in glucose homeostasis and insulin release, independent of GH secretion. Low plasma ghrelin levels are associated with elevated fasting insulin levels and insulin resistance, suggesting both physiological and pathophysiological roles for ghrelin. For this reason, at least theoretically, ghrelin and/or its signalling manipulation could be useful for the treatment or prevention of diseases of glucose homeostasis such as type 2 diabetes.
Highlights
GH is released from the pituitary gland in a pulsatile manner and it is mainly regulated by episodic changes in two hypothalamic hormones, growth hormone-releasing hormone (GHRH) and somatostatin
The first evidences about an interaction between ghrelin and glucose metabolism arose when it was seen that single subcutaneous ghrelin injections induced an increase of the respiratory quotient (RQ), which suggested an augmented utilization of carbohydrate and reduced utilization of fat to meet energy requirements that was congruent with the observed increase in body fat [10]
This insulin secretagogue effect of UAG was marked in the portal vein, whereas it was scarcely detectable in the systemic circulation, suggesting that UAG plays an important role in glucose metabolism in the liver
Summary
GH is released from the pituitary gland in a pulsatile manner and it is mainly regulated by episodic changes in two hypothalamic hormones, growth hormone-releasing hormone (GHRH) and somatostatin. The first evidences about an interaction between ghrelin and glucose metabolism arose when it was seen that single subcutaneous ghrelin injections induced an increase of the respiratory quotient (RQ), which suggested an augmented utilization of carbohydrate and reduced utilization of fat to meet energy requirements that was congruent with the observed increase in body fat [10] Another evidence that suggested that ghrelin could affect glucose metabolism was the fact that it stimulated acid secretion through vagal mediation [61, 62] and some studies suggested that the parasympathetic nerves that regulate hormonal control of insulin pass through the cervical vagus and the hepatic branch, and that the hepatic vagus nerve is important for the regulation of hepatic glucose production in the post absorptive state [63, 64]. In this work we will review the results obtained by different investigators about the relation between ghrelin and glucose metabolism and insulin release as well as its possible therapeutic role in disease states like diabetes
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