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  • 1
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    Online Resource
    Acute Effects of Ghrelin Administration on Glucose and Lipid Metabolism
    The Endocrine Society ; 2008
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 2 ( 2008-02-01), p. 438-444
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 93, No. 2 ( 2008-02-01), p. 438-444
    Abstract: Context: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. Objective: Our objective was to study direct effects of ghrelin on substrate metabolism. Design: This was a randomized, single-blind, placebo-controlled two-period crossover study. Setting: The study was performed in a university clinical research laboratory. Participants: Eight healthy men aged 27.2 ± 0.9 yr with a body mass index of 23.4 ± 0.5 kg/m2 were included in the study. Intervention: Subjects received infusion of ghrelin (5 pmol·kg−1·min−1) or placebo for 5 h together with a pancreatic clamp (somatostatin 330 μg·h−1, insulin 0.1 mU·kg−1·min−1, GH 2 ng·kg−1·min−1, and glucagon 0.5 ng·kg−1·min−1). A hyperinsulinemic (0.6 mU·kg−1·min−1) euglycemic clamp was performed during the final 2 h of each infusion. Results: Basal and insulin-stimulated glucose disposal decreased with ghrelin [basal: 1.9 ± 0.1 (ghrelin) vs. 2.3 ± 0.1 mg·kg−1·min−1, P = 0.03; clamp: 3.9 ± 0.6 (ghrelin) vs. 6.1 ± 0.5 mg·kg−1·min−1, P = 0.02], whereas endogenous glucose production was similar. Glucose infusion rate during the clamp was reduced by ghrelin [4.0 ± 0.7 (ghrelin) vs. 6.9 ± 0.9 mg·kg−1·min−1; P = 0.007] , whereas nonesterified fatty acid flux increased [131 ± 26 (ghrelin) vs. 69 ± 5 μmol/min; P = 0.048] in the basal period. Regional lipolysis (skeletal muscle, sc fat) increased insignificantly with ghrelin infusion. Energy expenditure during the clamp decreased after ghrelin infusion [1539 ± 28 (ghrelin) vs. 1608 ± 32 kcal/24 h; P = 0.048] , but the respiratory quotient did not differ. Minor but significant elevations in serum levels of GH and cortisol were observed after ghrelin infusion. Conclusions: Administration of exogenous ghrelin causes insulin resistance in muscle and stimulates lipolysis; these effects are likely to be direct, although a small contribution of GH and cortisol cannot be excluded.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2007-2018
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2008
    detail.hit.zdb_id: 2026217-6
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  • 2
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    Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients
    The Endocrine Society ; 2019
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 104, No. 7 ( 2019-07-01), p. 2581-2592
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 104, No. 7 ( 2019-07-01), p. 2581-2592
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2018-02503
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
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  • 3
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    Effects of free fatty acids, growth hormone and growth hormone receptor blockade on serum ghrelin levels in humans
    Wiley ; 2007
    In:  Clinical Endocrinology Vol. 66, No. 5 ( 2007-05), p. 641-645
    Details
    In: Clinical Endocrinology, Wiley, Vol. 66, No. 5 ( 2007-05), p. 641-645
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    URL: Article
    DOI: 10.1111/cen.2007.66.issue-5
    DOI: 10.1111/j.1365-2265.2007.02786.x
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2007
    detail.hit.zdb_id: 2004597-9
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  • 4
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    Ghrelin Does Not Directly Stimulate Secretion of Glucagon-like Peptide-1
    The Endocrine Society ; 2020
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 105, No. 1 ( 2020-01-01), p. 266-275
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 105, No. 1 ( 2020-01-01), p. 266-275
    Abstract: The gastrointestinal hormone ghrelin stimulates growth hormone secretion and appetite, but recent studies indicate that ghrelin also stimulates the secretion of the appetite-inhibiting and insulinotropic hormone glucagon-like peptide-1 (GLP-1). Objective To investigate the putative effect of ghrelin on GLP-1 secretion in vivo and in vitro. Subjects and Methods A randomized placebo-controlled crossover study was performed in eight hypopituitary subjects. Ghrelin or saline was infused intravenously (1 pmol/min × kg) after collection of baseline sample (0 min), and blood was subsequently collected at time 30, 60, 90, and 120 minutes. Mouse small intestine was perfused (n = 6) and GLP-1 output from perfused mouse small intestine was investigated in response to vascular ghrelin administration in the presence and absence of a simultaneous luminal glucose stimulus. Ghrelin receptor expression was quantified in human (n = 11) and mouse L-cells (n = 3) by RNA sequencing and RT-qPCR, respectively. Results Ghrelin did not affect GLP-1 secretion in humans (area under the curve [AUC; 0–120 min]: ghrelin infusion = 1.37 ± 0.05 min × nmol vs. saline infusion = 1.40 ± 0.06 min × nmol [P = 0.63] ), but induced peripheral insulin resistance. Likewise, ghrelin did not stimulate GLP-1 secretion from the perfused mouse small intestine model (mean outputs during baseline/ghrelin infusion = 19.3 ± 1.6/25.5 ± 2.0 fmol/min, n = 6, P = 0.16), whereas glucose-dependent insulinotropic polypeptide administration, used as a positive control, doubled GLP-1 secretion (P & lt; 0.001). Intraluminal glucose increased GLP-1 secretion by 4-fold (P & lt; 0.001), which was not potentiated by ghrelin. Finally, gene expression of the ghrelin receptor was undetectable in mouse L-cells and marginal in human L-cells. Conclusions Ghrelin does not interact directly with the L-cell and does not directly affect GLP-1 secretion.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/clinem/dgz046
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2026217-6
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  • 5
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    Constant intravenous ghrelin infusion in healthy young men: clinical pharmacokinetics and metabolic effects
    American Physiological Society ; 2007
    In:  American Journal of Physiology-Endocrinology and Metabolism Vol. 292, No. 6 ( 2007-06), p. E1829-E1836
    Details
    In: American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 292, No. 6 ( 2007-06), p. E1829-E1836
    Abstract: Ghrelin levels fluctuate rapidly and dynamically with surges before meal times and postprandial troughs, and ghrelin increases appetite and food intake. Circulating ghrelin correlates negatively with body mass index (BMI), but obese individuals have a reduced postprandial decrease in ghrelin levels. Whether this reflects changes in secretion or clearance of ghrelin is uncertain. We therefore studied the pharmacokinetics of ghrelin in relation to anthropometric and biochemical measures. We also studied the effects of ghrelin on hormones and metabolites. In fasting humans, we used a constant infusion rate of ghrelin lasting 180 min at 5 pmol·kg body wt −1 ·min −1 in a randomized, double-blind, placebo-controlled crossover study. Serum ghrelin (s-ghrelin; total levels) was distributed and eliminated according to a two-compartment model. s-Ghrelin initial half-life was 24 ± 2 min and terminal half-life 146 ± 36 min, respectively. Mean residence time (MRT) of ghrelin was 93 ± 16 min. MRT correlated positively with both BMI ( r = 0.51, P 〈 0.001) and high-density cholesterol (HDL) levels ( r = 0.75, P 〈 0.001). Serum insulin levels remained constant during ghrelin infusion, whereas plasma glucose increased 0.3 ± 0.1 mmol/l ( P 〈 0.01) and free fatty acid levels more than doubled (to 1.03 ± 0.08 mmol/l, P 〈 0.001), translating into a significant reduction of insulin sensitivity ( P 〈 0.001). In conclusion, 1) we describe novel pharmacokinetics of ghrelin that are useful when tailoring ghrelin infusion rates in clinical experiments, 2) BMI and HDL correlate positively with MRT of infused ghrelin, and 3) supraphysiological ghrelin levels impair insulin sensitivity.
    Type of Medium: Online Resource
    ISSN: 0193-1849 , 1522-1555
    URL: Article
    DOI: 10.1152/ajpendo.00682.2006
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477331-4
    SSG: 12
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  • 6
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    Free fatty acids decrease circulating ghrelin concentrations in humans
    Oxford University Press (OUP) ; 2006
    In:  European Journal of Endocrinology Vol. 154, No. 5 ( 2006-05), p. 667-673
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 154, No. 5 ( 2006-05), p. 667-673
    Abstract: Objective : Concentrations of the orexigenic peptide ghrelin is affected by a number of hormones, which also affect circulating levels of free fatty acids (FFAs). The present study was therefore designed to determine the direct effect of FFAs on circulating ghrelin. Design : Eight lean, healthy men were examined for 8 h on four occasions using variable infusion rates (0, 3, 6 and 12 μl/kg per min) of intralipid to create different plasma FFA concentrations. Constant levels of insulin and GH were obtained by administration of acipimox (250 mg) and somatostatin (300 μg/h). At the end of each study day a hyperinsulinaemic-euglycaemic clamp was performed. Results : Four distinct levels of FFAs were obtained at the end of the lipid infusion period (FFA LIPID : 0.03 ± 0.00 vs: 0.49 ± 0.04, 0.92 ± 0.08 and 2.09 ± 0.38 mmol/l; ANOVA P 〈 0.0001) and during hyperinsulinaemia (FFA LIPID+INSULIN : 0.02 ± 0.00 vs: 0.34 ± 0.03, 0.68 ± 0.09 and 1.78 ± 0.32 mmol/l; ANOVA P 〈 0.0001). Whereas, somatostatin infusion alone reduced ghrelin concentration by ~67%, concomitant administration of increasing amounts of intralipid reduced circulating ghrelin by a further 14, 19 and 19% respectively (change in ghrelin: 0.52 ± 0.05 vs: 0.62 ± 0.06, 0.72 ± 0.09 and 0.71 ± 0.05 μg/l; ANOVA P = 0.04). No further reduction in ghrelin concentration was observed during hyperinsulinaemia. Conclusion : FFA exposure between 0 and 1 mmol/l significantly suppresses ghrelin levels independent of ambient GH and insulin levels.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/eje.1.02146
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2006
    detail.hit.zdb_id: 1485160-X
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  • 7
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    Serum Ghrelin Levels Are Increased in Hypothyroid Patients and Become Normalized by l-Thyroxine Treatment
    The Endocrine Society ; 2008
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 6 ( 2008-06-01), p. 2277-2280
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 93, No. 6 ( 2008-06-01), p. 2277-2280
    Abstract: Context: An interaction between ghrelin, which is implicated in the regulation of short- and long-term energy balance, and thyroid function has been reported in hyperthyroidism in which ghrelin levels are reversibly suppressed. We measured serum ghrelin levels and metabolic indices in hypothyroid patients before and after l-thyroxine replacement. Patients and Methods: Eleven patients were examined twice: 1) in the hypothyroid state and 2) after at least 2 months of euthyroidism. Ten healthy subjects served as a control group. Ghrelin was measured in conjunction with indirect calorimetry and a hyperinsulinemic euglycemic clamp. Results: Serum ghrelin levels were increased by 32% under basal conditions in the hypothyroid state (PRE) as compared with posttreatment (POST) (picograms per milliliter): 976.4 ± 80.8 vs. 736.8 ± 67.1 (P & lt; 0.001). This difference prevailed during the clamp, but a decline was observed in both states: 641.4 ± 82.2 vs. 444.3 ± 66.8 μg/ml (P = 0.005). The hypothyroid state was associated with decreased resting energy expenditure, increased respiratory quotient, and insulin resistance. Serum ghrelin levels as well as the metabolic aberrations became normalized after l-thyroxine replacement as compared with the control subjects. Conclusion: Serum ghrelin levels are reversibly increased in hypothyroid patients. It remains to be investigated whether this represents a direct effect of iodothyronines on ghrelin secretion or clearance or a compensatory response to the abnormal energy metabolism in hypothyroid patients.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2007-2619
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2008
    detail.hit.zdb_id: 2026217-6
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  • 8
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    Unacylated Ghrelin Does Not Acutely Affect Substrate Metabolism or Insulin Sensitivity in Men With Type 2 Diabetes
    The Endocrine Society ; 2019
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 104, No. 6 ( 2019-06-01), p. 2435-2442
    Details
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 104, No. 6 ( 2019-06-01), p. 2435-2442
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    URL: Article
    DOI: 10.1210/jc.2018-02601
    RVK:
    XA 10000
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
    detail.hit.zdb_id: 2026217-6
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  • 9
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    Increased lipolysis after infusion of acylated ghrelin: a randomized, double‐blinded placebo‐controlled trial in hypopituitary patients
    Wiley ; 2020
    In:  Clinical Endocrinology Vol. 93, No. 6 ( 2020-12), p. 672-677
    Details
    In: Clinical Endocrinology, Wiley, Vol. 93, No. 6 ( 2020-12), p. 672-677
    Abstract: Acylated ghrelin increases growth hormone (GH) and adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary gland. Additionally, it increases free fatty acid levels independently of GH and ACTH, but the impact of ghrelin on fatty acid turnover has not been determined. This study was designed to test whether acylated ghrelin directly increases the turnover rate of fatty acids. Design Eight hypopituitary patients on stable replacement with GH and hydrocortisone were included in a randomized, double‐blinded, placebo‐controlled crossover study including two study days: (a) infusion of acylated ghrelin and (b) infusion of saline. The study day comprised a basal period ( t  = 0‐120 minutes) and a hyperinsulinaemic‐euglycemic clamp period ( t  = 120‐300 minutes). Whole‐body lipolysis was estimated at t  = 90‐120 and t  = 270‐300 minutes with a palmitate isotope dilution technique. Results Infusion of acylated ghrelin resulted in 10 times increased total ghrelin area under the curve (AUC) levels in the basal period and 15 times increased AUC levels in the clamp period compared with saline infusion ( P   〈  .001). GH AUC levels were largely unaffected by ghrelin compared to saline infusion during both the basal and clamp period, but cortisol AUC levels increased by 15% after ghrelin compared to saline infusion in the basal period ( P  = .03). Palmitate turnover was increased by 43% in the basal period (difference: 77 (20) µmol/min, P  = .01) and unchanged in the clamp period (difference 0.9 (17) µmol/min, P  = 1.0) after ghrelin compared to saline infusion. Conclusions Our results support the hypothesis that pharmacological levels of acylated ghrelin directly activate lipolysis at the whole‐body level.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    URL: Article
    DOI: 10.1111/cen.v93.6
    DOI: 10.1111/cen.14290
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2004597-9
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  • 10
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    Cardiovascular effects of intravenous ghrelin infusion in healthy young men
    American Physiological Society ; 2007
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 293, No. 5 ( 2007-11), p. H3020-H3026
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 293, No. 5 ( 2007-11), p. H3020-H3026
    Abstract: Ghrelin infusion improves cardiac function in patients suffering from cardiac failure, and bolus administration of ghrelin increases cardiac output in healthy subjects. The cardiovascular effects of more continuous intravenous ghrelin exposure remain to be studied. We therefore studied the cardiovascular effects of a constant infusion of human ghrelin at a rate of 5 pmol/kg per minute for 180 min. Fifteen healthy, young (aged 23.2 ± 0.5 yr), normal-weight (23.0 ± 0.4 kg/m 2 ) men volunteered in a randomized double-blind, placebo-controlled crossover study. With the subjects remaining fasting, peak myocardial systolic velocity S′, tissue tracking TT, left ventricular ejection fraction EF, and endothelium-dependent flow-mediated vasodilatation were measured. Ghrelin infusion increased S′ 9% ( P = 0.002) and TT 10% ( P 〈 0.001), whereas EF, resting blood flow velocity, and endothelium-dependent flow-mediated vasodilatation did not change ( P = 0.13). This was associated with a peak in serum growth hormone after 60 min of infusion (37.77 ± 5.27 ng/ml, P 〈 0.001), a doubling of free fatty acid levels ( P = 0.001), and a 1.6-fold increase in cortisol levels ( P 〈 0.05), whereas glucose and catecholamine levels were constant. In conclusion, supraphysiological levels of ghrelin stimulate left ventricular function in terms of S′ and TT in healthy young normal-weight men without changing resting blood flow velocity and endothelium-dependent flow-mediated vasodilatation. The effects did not translate into detectable increments in EF.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.00496.2007
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2007
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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