Administration of Acylated Ghrelin Reduces Insulin Sensitivity, Whereas the Combination of Acylated Plus Unacylated Ghrelin Strongly Improves Insulin Sensitivity

Gauna, C.; Meyler, F. M.; Janssen, Joseph A M J L; Delhanty, Patric J. D.; Abribat, Thierry; Koetsveld, Peter van; Hofland, Leo J.; Broglio, Fabio; Ghigo, Ezio; Lely, Aart Jan van der

doi:10.1210/jc.2004-0363

Cited by 230 publications

(234 citation statements)

References 55 publications

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“…Emerging evidence suggests that AG and UAG exert different physiological effects on appetite control and glucose metabolism (4)(5)(6)(7). AG has been reported to stimulate food intake, whereas UAG does not seem to have an orexigenic effect (7).…”

Section: Introductionmentioning

confidence: 99%

“…AG has been reported to stimulate food intake, whereas UAG does not seem to have an orexigenic effect (7). AG is associated with reduced insulin sensitivity, whereas co-administration of UAG with AG seems to improve insulin sensitivity (5,8). Whether AG and UAG also have different roles in body weight, body composition, and adiposity remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Unacylated ghrelin is associated with changes in body composition and body fat distribution during long-term exercise intervention

Cederberg

Rajala

Koivisto

et al. 2011

European Journal of Endocrinology

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Objective: Ghrelin, a gut-brain peptide involved in energy homeostasis, circulates predominantly (O90%) in unacylated form. Previous studies, however, have focused on total and acylated ghrelin, and the role of unacylated ghrelin (UAG) is not well understood. Particularly, the association of UAG with weight loss and changes in body composition in adults remains unclear. We hypothesized that exercise-associated increase in UAG level is associated with weight loss, favorable changes in body composition, and body fat distribution. Design and methods: A prospective study of 552 young men (mean age 19.3 and range 19-28 years) undergoing military service with structured 6-month exercise training program. Exercise performance, body composition, and biochemical measurements were obtained at baseline and follow-up. Association between changes in UAG levels and body composition and body fat distribution were evaluated. Results: An increase in UAG level during the exercise intervention was associated with reduced weight, fat mass (FM), fat percentage (fat %), and waist circumference, but not with fat-free mass. Inverse associations of changes in UAG level with changes in waist circumference and fat % were independent of weight at baseline, and changes in weight and exercise performance. Associations of changes in UAG level with waist circumference were significantly stronger than with fat % after the adjustment for confounding variables. Conclusion: UAG is associated with changes in body weight and body composition during an intensive long-term exercise intervention in young men. The association of UAG levels with changes in central obesity was stronger than with total FM.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Unacylated ghrelin is associated with changes in body composition and body fat distribution during long-term exercise intervention

Cederberg

Rajala

Koivisto

et al. 2011

European Journal of Endocrinology

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“…This suggests the presence of very high serum levels of desacyl ghrelin in our patients, even if we could not definitely exclude the presence of circulating degradation products of mature ghrelin peptides. Several mechanisms may therefore be hypothesized to explain the absence of functional consequences of ghrelin overproduction in our patients, such as: i) competition between desacyl ghrelin and acyl ghrelin, as previously suggested on experimental grounds (4,(18)(19)(20)(21) and ii) interference with other mechanisms contributing to the regulation of appetite and the induction of cachexia in patients with advanced cancer, such as inflammatory cytokines and adipokines. The limited amount of tumor tissue available for study in our patients and the absence of frozen tissue prevented the possibility to analyze in depth the expression and metabolism of ghrelin in tumor tissues and to evaluate the expression of its specific receptors.…”

Section: Discussionmentioning

confidence: 67%

Major hyperghrelinemia in advanced well-differentiated neuroendocrine carcinomas: report of three cases

Walter

Chardon²,

Hervieu³

et al. 2009

European Journal of Endocrinology

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Objective: We aimed to gain insight into the functional consequences of ghrelin overproduction in patients with neuroendocrine tumors and its relations with disease characteristics and evolution. Design: We retrospectively analyzed three cases of neuroendocrine carcinomas associated with very high levels of circulating ghrelin. Methods: Between February and October 2007, serum ghrelin levels were determined in all patients with well-differentiated endocrine carcinoma referred to our center (nZ72). Three patients were found to have circulating ghrelin levels O10-fold the upper limit of normal. The clinical, biochemical, and pathological characteristics of these three patients were reviewed. The ratio between circulating acyl and total ghrelin was determined, and tumor tissue expression of ghrelin was assayed by immunohistochemistry. Results: The three patients had massive hyperghrelinemia (respectively 49 028, 63 711, and 101 996 pg/ml), with !10% of acyl ghrelin. The corresponding primary tumors were located in the pancreas, rectum, and gallbladder; all were metastatic. There was no acromegaly; there was a decrease in appetite; and body mass index was low. Serum GH levels were only slightly increased and serum IGF1 levels were normal. Immunoreactive ghrelin was detected in the tumor tissue in the two cases in which tissue material was available. All three patients died before 12 months after the diagnosis of hyperghrelinemia. Conclusion: Well-differentiated neuroendocrine carcinomas of various origins may produce markedly high levels of circulating ghrelin, without evidence of clinical or functional consequences.

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“…Initial studies with ghrelin in humans attempted to control for ghrelin's secondary GH release, using either infusion of somatostatin to inhibit GH release, or GH‐deficient participants (Gauna et al. 2004; Vestergaard et al. 2008a).…”

Section: Discussionmentioning

confidence: 99%

Acylated and unacylated ghrelin do not directly stimulate glucose transport in isolated rodent skeletal muscle

Cervone

Dyck

2017

Physiol Rep

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Emerging evidence implicates ghrelin, a gut‐derived, orexigenic hormone, as a potential mediator of insulin‐responsive peripheral tissue metabolism. However, in vitro and in vivo studies assessing ghrelin's direct influence on metabolism have been controversial, particularly due to confounding factors such as the secondary rise in growth hormone (GH) after ghrelin injection. Skeletal muscle is important in the insulin‐stimulated clearance of glucose, and ghrelin's exponential rise prior to a meal could potentially facilitate this. This study was aimed at elucidating any direct stimulatory action that ghrelin may have on glucose transport and insulin signaling in isolated rat skeletal muscle, in the absence of confounding secondary factors. Oxidative soleus and glycolytic extensor digitorum longus skeletal muscles were isolated from male Sprague Dawley rats in the fed state and incubated with various concentrations of acylated and unacylated ghrelin in the presence or absence of insulin. Ghrelin did not stimulate glucose transport in either muscle type, with or without insulin. Moreover, GH had no acute, direct stimulatory effect on either basal or insulin‐stimulated muscle glucose transport. In agreement with the lack of observed effect on glucose transport, ghrelin and GH also had no stimulatory effect on Ser473 AKT or Thr172 AMPK phosphorylation, two key signaling proteins involved in glucose transport. Furthermore, to our knowledge, we are among the first to show that ghrelin can act independent of its receptor and cause an increase in calmodulin‐dependent protein kinase 2 (CaMKII) phosphorylation in glycolytic muscle, although this was not associated with an increase in glucose transport. We conclude that both acylated and unacylated ghrelin have no direct, acute influence on skeletal muscle glucose transport. Furthermore, the immediate rise in GH in response to ghrelin also does not appear to directly stimulate glucose transport in muscle.

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Administration of Acylated Ghrelin Reduces Insulin Sensitivity, Whereas the Combination of Acylated Plus Unacylated Ghrelin Strongly Improves Insulin Sensitivity

Cited by 230 publications

References 55 publications

Unacylated ghrelin is associated with changes in body composition and body fat distribution during long-term exercise intervention

Unacylated ghrelin is associated with changes in body composition and body fat distribution during long-term exercise intervention

Major hyperghrelinemia in advanced well-differentiated neuroendocrine carcinomas: report of three cases

Acylated and unacylated ghrelin do not directly stimulate glucose transport in isolated rodent skeletal muscle

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