Circulating ghrelin levels in basal conditions and during glucose tolerance test in acromegalic patients

Cappiello, Vincenzo; Ronchi, Cristina L.; Morpurgo, Paola S.; Epaminonda, Paolo; Arosio, Maura; Beck‐Peccoz, Paolo; Spada, Anna

doi:10.1530/eje.0.1470189

Cited by 83 publications

(87 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The same pattern was observed by analyzing other adipose tissue regulatory peptides. In this study, the levels of ghrelin, an acylpeptide gut -brain hormone that negatively correlates with fasting insulin and/or insulin resistance (32,33), was found to positively correlate with ApN levels in healthy controls, while this relationship was absent in the acromegalic group. Taken together, these data suggest that the changes in ApN, and possibly resistin, do not contribute to insulin resistance in acromegaly.…”

Section: Discussionmentioning

confidence: 58%

Circulating adiponectin levels and cardiovascular risk factors in acromegalic patients

Ronchi

Corbetta

Cappiello

et al. 2004

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Objective: Adiponectin (ApN) is an adipocytokine expressed in human adipose cells with anti-atherogenic and anti-inflammatory properties that plays a role in the pathophysiology of insulin resistance, metabolic syndrome and coronary artery disease. The aim of the study was to evaluate ApN secretion in patients with acromegaly, a chronic disease associated with insulin resistance and increased cardiovascular mortality, and to correlate ApN levels with hormonal, metabolic and cardiovascular parameters. Design and methods: The study included 32 patients with active acromegaly (11 male and 21 female, aged 48^11 years, duration of disease: 8^6 years, GH: 9.2^9.8 mg/l, IGF-I: 80^33 nmol/l (meansŜ .D.)) and 38 control subjects sex-and body mass index (BMI)-matched. In all subjects, serum ApN, leptin and ghrelin levels, BMI, waist circumference, insulin resistance (assessed by homeostasis model assessment and the quantitative insulin check index), lipid profile and blood pressure values were evaluated. Results: Acromegalic patients and control subjects had similar ApN levels (9.4^3.5 vs 9.5^4.0 mg/l, NS), while when considering obese subjects acromegalic patients had ApN levels significantly higher than controls (10.2^4 vs 7.5^3 mg/l, P , 0.05). No significant correlation between ApN and GH/IGF-I levels or duration of disease was found. ApN concentrations negatively correlated with BMI, waist circumference, glucose and diastolic blood pressure and positively with high-density lipoprotein cholesterol and ghrelin in controls, while all these correlations were lost in acromegalic patients. Conclusions: We provide evidence that, although metabolic and cardiovascular abnormalities are present in most acromegalic patients, in these subjects ApN levels are not reduced and, contrary to what is found in BMI-matched controls, do not correlate with cardiovascular risk factors. These data support the view that atherosclerosis is not the main determinant of cardiovascular mortality in acromegaly and suggest a permissive action of GH and/or IGF-I excess on ApN secretion.

show abstract

Section: Discussionmentioning

confidence: 58%

Circulating adiponectin levels and cardiovascular risk factors in acromegalic patients

Ronchi

Corbetta

Cappiello

et al. 2004

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Both GH deficiency and excess are associated with an increased risk of atherosclerosis. Acromegaly is associated with both low HDL levels (11) and low ghrelin levels (12). GH deficiency is associated with low ghrelin levels (13), but it is unclear whether there are changes in HDL levels in these patients (10,14).…”

Section: Ghrelin Interacting With a Species Of Hdl 8878mentioning

confidence: 99%

Ghrelin Can Bind to a Species of High Density Lipoprotein Associated with Paraoxonase

Beaumont¹,

Skinner²,

Tan³

et al. 2003

Journal of Biological Chemistry

135

View full text Add to dashboard Cite

Ghrelin is a 28-residue peptide hormone that is principally released from the stomach during fasting and prior to eating. Two forms are present in human plasma: the unmodified peptide and a less abundant acylated version, in which octanoic acid is attached to the third residue, a serine, via an ester linkage. The acylated form of ghrelin acts as a ligand for the growth hormone secretagogue receptor and can stimulate the release of growth hormone from the pituitary gland. It also initiates behavioral and metabolic adaptations to fasting. Here we show that an immobilized form of ghrelin specifically binds a species of high density lipoprotein associated with the plasma esterase, paraoxonase, and clusterin. Both free ghrelin and paraoxon, a substrate for paraoxonase, can inhibit this interaction. An endogenous species of ghrelin is found to co-purify with high density lipoprotein during density gradient centrifugation and subsequent gel filtration. This interaction links the orexigenic peptide hormone ghrelin to lipid transport and metabolism. Furthermore, the interaction of the esterified hormone ghrelin with a species of HDL containing an esterase suggests a possible mechanism for the conversion of ghrelin to des-acyl ghrelin.Ghrelin is a peptide hormone that was purified from the stomach that can cause the release of growth hormone from the anterior pituitary gland (1). It has subsequently been found that ghrelin is predominantly released from the stomach prior to feeding (2), although other tissues have been shown to express the gene as well (3). Peripheral injections of ghrelin have been shown to increase feeding in both rats (4) and humans (5), and a course of injections leads to increased obesity in rats (4). Therefore, ghrelin can be seen as an important link between the stomach, appetite, and metabolism as well as playing a role in growth hormone release.The aim of this study was to establish whether ghrelin interacts with any other component of plasma. It was hypothesized that any interaction might be an important factor in determining the activity or longevity of ghrelin in plasma. Furthermore, an interaction in the plasma might be involved in the creation of the two distinct forms of ghrelin (6): the acylated form, in which octanoic acid is covalently bound to the peptide, and the more prevalent des-acyl form in which the peptide is unmodified. The acylated form of ghrelin stimulates the release of growth hormone from the pituitary gland, therefore any mechanism that might convert one form of ghrelin into the other could be an important factor in controlling the activity of ghrelin. MATERIALS AND METHODSA peptide corresponding to mature human ghrelin, with a cysteine residue substituted for the serine residue at the third position (S3C ghrelin), was synthesized by Fmoc 1 chemistry using a Rainin PS3 automatic peptide synthesizer (Protein Technologies). The peptide was purified to over 90% homogeneity by reverse-phase chromatography using a Varian 500LC HPLC. The molecular weight of the purified peptide ...

show abstract

“…However, the increased GH secretion observed during conditions such as exercise (1), fasting (2), and hypoglycemia (3), does not appear to be subserved by ghrelin. If anything, data obtained in acromegaly (4,5) and following GH administration (6,7) indicate that GH to a moderate extent suppresses systemic ghrelin levels. By contrast, the circadian pattern of ghrelin is closely associated with food intake with high preprandial levels, a postprandial suppression, and intermediary and more stable nocturnal concentrations (8).…”

Section: Introductionmentioning

confidence: 99%

Effects of GH replacement therapy in adults on serum levels of leptin and ghrelin: the role of lipolysis

et al. 2005

View full text Add to dashboard Cite

Objective: The regulation and function of systemic ghrelin levels appear to be associated with food intake and energy balance rather than GH. Since GH, in turn, acutely induces lipolysis and insulin resistance in skeletal muscle, we aimed to study the isolated and combined effects of GH, free fatty acids (FFAs) and insulin sensitivity on circulating ghrelin levels in human subjects. Design: Seven GH-deficient patients (aged 37^4 years (mean^S.E.)) were studied on four occasions in a 2 £ 2 factorial design with and without GH substitution and with and without administration of acipimox, which lowers FFA levels by inhibition of the hormone-sensitive lipase, in the basal state and during a hyperinsulinemic euglycemic clamp. Results: Serum FFA levels decreased with acipimox administration irrespective of GH status. The GHinduced reduction in insulin sensitivity was countered by acipimox. Fasting ghrelin levels decreased insignificantly during GH administration alone, but were reduced by 33% during co-administration of GH and acipimox (Aci) (in ng/l): 860^120 (2 GH 2 Aci), 711^130 (2 GH þ Aci), 806^130 (þGH 2 Aci), 574^129 (þGH þ Aci), P , 0.01. The clamp was associated with a further, moderate lowering of ghrelin. GH and acipimox induced a reciprocal 25% increase in serum leptin levels (mg/l): 11.2^4.4 (2GH 2 Aci), 11.7^4.4 (2 GH þ Aci), 11.5^4.4 (þGH 2 Aci), 13.9^4.2 (þGH þ Aci), P ¼ 0.005. Conclusion: Our data suggest that antilipolysis via suppression of the hormone-sensitive lipase in combination with GH administration is associated with significant and reciprocal changes in ghrelin and leptin.European Journal of Endocrinology 153 545-549

show abstract

Circulating ghrelin levels in basal conditions and during glucose tolerance test in acromegalic patients

Cited by 83 publications

References 34 publications

Circulating adiponectin levels and cardiovascular risk factors in acromegalic patients

Circulating adiponectin levels and cardiovascular risk factors in acromegalic patients

Ghrelin Can Bind to a Species of High Density Lipoprotein Associated with Paraoxonase

Effects of GH replacement therapy in adults on serum levels of leptin and ghrelin: the role of lipolysis

Contact Info

Product

Resources

About