Acylated Ghrelin Secretion Is Acutely Suppressed by Oral Glucose Load or Insulin-Induced Hypoglycemia Independently of Basal Growth Hormone Secretion in Humans

Abstract

Background: Ghrelin has been reported to be the natural ligand of growth hormone (GH) secretagogue receptor, and it is known that exogenous ghrelin administration strongly stimulates GH release in humans. However, the effects of endogenous ghrelin on GH secretion and changes in ghrelin levels during dynamic changes in GH levels are not well understood. Methods: Therefore, we measured circulating acylated ghrelin concentrations during oral glucose tolerance tests (OGTTs) in patients with active acromegaly (AA, n = 9) and in age/sex/BMI-matched group A controls (n = 12), and during insulin tolerance testing (ITT) in patients with GH deficiency (GHD, n = 10) and in group B controls (n = 10). Plasma acylated ghrelin, serum GH, insulin and glucose levels were measured during each test. Results: Fasting plasma ghrelin levels correlated negatively with serum insulin levels in both group A and B controls (r = –0.665; p < 0.05) but not in patients with AA or GHD. During OGTTs, circulating ghrelin levels decreased significantly with a nadir at 30 min in both patients with AA (p < 0.05) and group A controls (p < 0.01). Also, ITTs were followed by a significant decrease in circulating ghrelin levels with a nadir at 30 min in patients with GHD (p < 0.05) and in group B controls (p < 0.05). Conclusion: The results of the study show that at baseline acylated ghrelin levels do not differ with respect to the GH status (GH excess or GH deficiency) and, furthermore, the suppression of acylated ghrelin levels during OGTT or ITT is independent of the GH response to the tests.

Circulating acylghrelin levels are suppressed by insulin and increase in response to hypoglycemia in healthy adult volunteers

“…Taken together, it would be teleologically meaningful if AG levels are suppressed by insulin and stimulated by hypoglycemia. This study demonstrates that AG and UAG measured by updated assays are initially suppressed by hyperinsulinemia, which is in concordance with studies using older assays (8,9,10,11). Our study demonstrates an independent effect of acute hyperinsulinemia on both AG and UAG levels in the absence of a change in plasma glucose levels.…”

“…Among these effects, glucoregulatory properties seem to be important (5) and ghrelin-deficient mice developed profound hypoglycemia during calorie restriction (7). In response to insulin-induced hypoglycemia, however, total (8,9) as well as AG (10) and UAG (11) levels decrease rather than increase in human subjects, irrespective of GH status (12). Whether this discrepancy reflects reciprocal effects of insulin and hypoglycemia per se remains unclear.…”

Changes in total ghrelin within the somatotropic axis in severe burn patients: Comparison of those with inhalation injury and those without inhalation injury

“…However, it still remains to be elucidated which factor ultimately controls this stimulation of GH release in response to stress. Previous insulin tolerance test studies on total and acylated ghrelin demonstrated that insulin-induced hypoglycemia did not suppress the ghrelin secretion and GH might not be regulated by ghrelin [17][18][19]. In our study, GH levels were elevated whereas total ghrelin levels were decreased, and the total ghrelin levels were lower in the subjects with inhalation burn compared with the subjects without inhalation injury.…”

Influence of pegvisomant on serum ghrelin and leptin levels in acromegalic patients

“…It interacts with the GH secretagogue receptor type 1a (GHSR1a) and stimulates GH secretion. The ratio between both ghrelin forms (acylated and desacylated ghrelin) is calculated to be about 1 according to Moller et al The ratio between both ghrelin forms is closely maintained after food intake (41) or during oral glucose load (40). According to Kim et al (40), these findings are independent of GH levels.…”