Interactions of Gastrointestinal Peptides: Ghrelin and Its Anorexigenic Antagonists

Wisser, Anna-Sophia; Habbel, Piet; Wiedenmann, Bertram; Klapp, Burghard F.; Mönnikes, Hubert; Kobelt, Peter

doi:10.1155/2010/817457

Cited by 12 publications

(10 citation statements)

References 152 publications

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“…Ghrelin is the only known hormone synthesized in the gut and acting centrally that possesses an orexigenic effect (for reviews, see Depoortere, 2009;Castañ eda et al, 2010;Wisser et al, 2010;Briggs and Andrews, 2011;Nass et al, 2011;Scerif et al, 2011). In the adenohypophysis, ghrelin releases Ca 2ϩ from intracellular stores that stimulates and amplifies pulsatile secretion of growth hormone (GH) (Smith et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Characterization of New Stable Ghrelin Analogs with Prolonged Orexigenic Potency

Maletı́nská

Pýchová²,

Holubová³

et al. 2011

J Pharmacol Exp Ther

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Ghrelin, the only known peripherally produced and centrally acting peptide that stimulates food intake, is synthesized primarily in the stomach and acts through the growth hormone secretagogue receptor (GHS-R1a). In addition to its orexigenic effect, ghrelin stimulates the release of growth hormone (GH). In this study, we investigated the biological properties of fulllength and shortened ghrelin analogs in which octanoylated Ser 3 is replaced with an octanoic acid moiety coupled to diaminopropionic acid (Dpr). Ghrelin analogs stabilized with Dpr(N-octanoyl) in position 3 and noncoded amino acids in position 1 (sarcosine) and/or position 4 (naphthylalanine or cyclohexylalanine) were found to possess affinities similar to those of ghrelin for cell membranes with transfected GHS-R1a. In vivo, the prolonged orexigenic effects of analogs containing Dpr(N-octanoyl) 3 compared with that of ghrelin in adult mice and a similar impact on GH secretion in young mice were found. Full-length [Dpr(N-octanoyl) 3 ]ghrelin and its analogs with a noncoded amino acid in position 1 and/or 4 showed significantly prolonged stability in blood plasma compared with that of ghrelin. Ghrelin analogs with a prolonged orexigenic effect are potential treatments for GH deficiency or cachexia that accompanies chronic diseases. Desoctanoylated ghrelin analogs and N-terminal penta-and octapeptides of ghrelin did not show any biological activity.

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Section: Introductionmentioning

confidence: 99%

Characterization of New Stable Ghrelin Analogs with Prolonged Orexigenic Potency

Maletı́nská

Pýchová²,

Holubová³

et al. 2011

J Pharmacol Exp Ther

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“…The gut brain axis has been extensively implicated in human health. Hormones secreted by the gut have been shown to interact with the brain and regulate feeding behavior and energy balance [ 4 ]. Food intake behavior and energy homeostasis are strongly regulated by a complex system of humoral factors and neural structures constituting the gut-brain axis.…”

Section: Introductionmentioning

confidence: 99%

Ghrelin, Amylin, Gastric Inhibitory Peptide and Cognition in Middle-Aged HIV-Infected and Uninfected Women: The Women’s Interagency HIV Study

McFarlane

Mielke

Uglialoro

et al. 2017

J Neurol Neurophysiol

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Objective To explore the gut-brain axis by examining gut hormone levels and cognitive test scores in women with (HIV+) and without (HIV−) HIV infection. Design/methods Participants included 356 women (248 HIV+, 108 at risk HIV−) in the Brooklyn Women’s Interagency HIV Study (WIHS) with measured levels of ghrelin, amylin and gastric inhibitory peptide (GIP), also known as glucose-dependent insulinotropic polypeptide. Cross-sectional analyses using linear regression models estimated the relationship between gut hormones and Trails A, Trails B, Stroop interference time, Stroop word recall, Stroop color naming and reading, and Symbol Digit Modalities Test (SDMT) with consideration for age, HIV infection status, Wide Range Achievement Test score (WRAT), CD4 count, insulin resistance, drug use, and race/ethnicity. Results Among women at mid-life with chronic (at least 10 years) HIV infection or among those at risk, ghrelin, amylin and GIP were differentially related to cognitive test performance by cognitive domain. Better performance on cognitive tests was generally associated with higher ghrelin, amylin and GIP levels. However, the strength of association varied, as did significance level by HIV status. Conclusion Previous analyses in WIHS participants have suggested that higher BMI, waist, and WHR are associated with better cognitive function among women at mid-life with HIV infection. This study indicates that higher gut hormone levels are also associated with better cognition. Gut hormones may provide additional mechanistic insights regarding the association between obesity and Type 2 diabetes and cognition in middle-aged HIV+ and at risk HIV− women. In addition, measuring these hormones longitudinally would add to the understanding of mechanisms of actions of these hormones and their use as potential clinical tools for early identification and intervention on cognitive decline in this vulnerable population.

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“…Recent data indicate that the orexigenic effect of ghrelin might also be influenced by other gastrointestinal peptides such as cholecystokine (CCK), bombesin, peptide YY , and glucagon-like peptide-1 (GLP-1), suggesting relevant cross-talk among peripheral orexigenic and anorexigenic signals in the control of appetite and body weight (49).…”

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confidence: 99%

Metabolomic linkage reveals functional interaction between glucose-dependent insulinotropic polypeptide and ghrelin in humans

Rudovich

Nikiforova

Otto

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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-The gastric peptide ghrelin promotes energy storage, appetite, and food intake. Nutrient intake strongly suppresses circulating ghrelin via molecular mechanisms possibly involving insulin and gastrointestinal hormones. On the basis of the growing evidence that glucose-dependent insulinotropic polypeptide (GIP) is involved in the control of fuel metabolism, we hypothesized that GIP and/or insulin, directly or via changes in plasma metabolites, might affect circulating ghrelin. Fourteen obese subjects were infused with GIP (2.0 pmol·kg Ϫ1 ·min Ϫ1 ) or placebo in the fasting state during either euglycemic hyperinsulinemic (EC) or hyperglycemic hyperinsulinemic clamps (HC). Apart from analysis of plasma ghrelin and insulin levels, GC-TOF/MS analysis was applied to create a hormone-metabolite network for each experiment. The GIP and insulin effects on circulating ghrelin were analyzed within the framework of those networks. In the HC, ghrelin levels decreased in the absence (19.2% vs. baseline, P ϭ 0.028) as well as in the presence of GIP (33.8%, P ϭ 0.018). Ghrelin levels were significantly lower during HC with GIP than with placebo, despite insulin levels not differing significantly. In the GIP network combining data on GIPinfusion, ECϩGIP and HCϩGIP experiments, ghrelin was integrated into hormone-metabolite networks through a connection to a group of long-chain fatty acids. In contrast, ghrelin was excluded from the network of experiments without GIP. GIP decreased circulating ghrelin and might have affected the ghrelin system via modification of long-chain fatty acid pools. These observations were independent of insulin and offer potential mechanistic underpinnings for the involvement of GIP in systemic control of energy metabolism. obesity; euglycemic hyperinsulinemic clamp; hyperglycemic hyperinsulinemic clamp; time-of-flight gas chromatography-mass spectrometry analysis ENERGY HOMEOSTASIS and food intake behavior are regulated by a complex system of endocrine, neuronal, and nutrient signals including an increasingly well-understood communication channel called the brain-gut axis (42). Ghrelin, an acylated gut peptide that is primarily produced by endocrine cells of the gastric mucosa (22), stimulates food intake and promotes adiposity (43). Feeding suppresses ghrelin production and fasting stimulates ghrelin release (43, 44). The exact molecular basis for controlling these processes is still not entirely understood. Parenteral glucose and/or insulin infusions clearly suppress ghrelin levels when administered for prolonged periods or at supraphysiological doses in animals and in humans (2,14,26,31,40,47). Physiological doses of glucose and/or insulin that mimic postprandial fluctuations, however, do not seem to affect circulating ghrelin in humans (7,24,41). In contrast, enteral nutrients consistently suppress ghrelin levels even at low doses (2,14,24,40). Moreover, selective gastric distension, chemosensation, or nutrient exposure are insufficient to induce a ghrelin response in animals (6), whereas exposure...

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Interactions of Gastrointestinal Peptides: Ghrelin and Its Anorexigenic Antagonists

Cited by 12 publications

References 152 publications

Characterization of New Stable Ghrelin Analogs with Prolonged Orexigenic Potency

Characterization of New Stable Ghrelin Analogs with Prolonged Orexigenic Potency

Ghrelin, Amylin, Gastric Inhibitory Peptide and Cognition in Middle-Aged HIV-Infected and Uninfected Women: The Women’s Interagency HIV Study

Metabolomic linkage reveals functional interaction between glucose-dependent insulinotropic polypeptide and ghrelin in humans

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