Plasma levels of n-decanoyl ghrelin, another acyl- and active-form of ghrelin, in human subjects and the effect of glucose- or meal-ingestion on its dynamics

Yoh, Junko; Nishi, Yoshihiro; Hosoda, Hiroshi; Tajiri, Yuji; Yamada, Kentaro; Yanase, Toshihiko; Doi, Ryosuke; Yonemoto, Koji; Kangawa, Kenji; Kojima, Masayasu; Tanaka, Eiichiro; Kusukawa, Jingo

doi:10.1016/j.regpep.2010.12.010

Cited by 16 publications

(10 citation statements)

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“…The antiserum used for the total ghrelin RIA recognized all ghrelin peptides with intact C-terminal sequences irrespective of their N-terminal acylation, and exhibited complete cross-reactivity with human, mouse, and rat forms of ghrelin. Stomach or plasma samples for C8-ghrelin, C10-ghrelin, or total ghrelin RIA from mice were prepared as described previously (14, 25, 27). …”

Section: Methodsmentioning

confidence: 99%

Changes in Subcellular Distribution of n-Octanoyl or n-Decanoyl Ghrelin in Ghrelin-Producing Cells

Nishi¹,

Mifune²,

Yabuki³

et al. 2013

Front. Endocrinol.

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Background: The enzyme ghrelin O-acyltransferase (GOAT) catalyzes the acylation of ghrelin. The molecular form of GOAT, together with its reaction in vitro, has been reported previously. However, the subcellular processes governing the acylation of ghrelin remain to be elucidated.Methods: Double immunoelectron microscopy was used to examine changes in the relative proportions of secretory granules containing n-octanoyl ghrelin (C8-ghrelin) or n-decanoyl ghrelin (C10-ghrelin) in ghrelin-producing cells of mouse stomachs. The dynamics of C8-type (possessing C8-ghrelin exclusively), C10-type (possessing C10-ghrelin only), and mixed-type secretory granules (possessing both C8- and C10-ghrelin) were investigated after fasting for 48 h or after 2 weeks feeding with chow containing glyceryl-tri-octanoate (C8-MCT) or glyceryl-tri-decanoate (C10-MCT). The dynamics of C8- or C10-ghrelin-immunoreactivity (ir-C8- or ir-C10-ghrelin) within the mixed-type granules were also investigated.Results: Immunoelectron microscopic analysis revealed the co-existence of C8- and C10-ghrelin within the same secretory granules (mixed-type) in ghrelin-producing cells. Compared to control mice fed standard chow, the ratio of C10-type secretory granules increased significantly after ingestion of C10-MCT, whereas that of C8-type granules declined significantly under the same treatment. After ingestion of C8-MCT, the proportion of C8-type secretory granules increased significantly. Within the mixed-type granules the ratio of ir-C10-ghrelin increased significantly and that of ir-C8-ghrelin decreased significantly upon fasting.Conclusion: These findings confirmed that C10-ghrelin, another acyl-form of active ghrelin, is stored within the same secretory granules as C8-ghrelin, and suggested that the types of medium-chain acyl-molecules surrounding and available to the ghrelin-GOAT system may affect the physiological processes of ghrelin acylation.

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Section: Methodsmentioning

confidence: 99%

Changes in Subcellular Distribution of n-Octanoyl or n-Decanoyl Ghrelin in Ghrelin-Producing Cells

Nishi¹,

Mifune²,

Yabuki³

et al. 2013

Front. Endocrinol.

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“…It is also possible that the administration of basal insulin the night before by two of the MODY3 participants might have “normalized” their fasting profile, including ghrelin. Studies that reported acylated ghrelin levels in T2D subjects showed lower[16] or higher levels [15–44] compared to normoglycemic individuals. Therefore, whether acylated ghrelin levels are abnormal in T2D is controversial.…”

Section: Discussionmentioning

confidence: 99%

HNF1α defect influences post-prandial lipid regulation

et al. 2017

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PurposeHepatocyte nuclear factor 1 alpha (HNF1α) defects cause Mature Onset Diabetes of the Young type 3 (MODY3), characterized by defects in beta-cell insulin secretion. However, HNF1α is involved in many other metabolic pathways with relevance for monogenic or polygenic type 2 diabetes. We aimed to investigate gut hormones, lipids, and insulin regulation in response to a meal test in HNF1α defect carriers (MODY3) compared to non-diabetic subjects (controls) and type 2 diabetes (T2D).MethodsWe administered a standardized liquid meal to each participant. Over 6 hours, we measured post-meal responses of insulin regulation (blood glucose, c-peptide, insulin), gut hormones (ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1) and lipids (non-esterified fatty acids [NEFA] and triglycerides).ResultsWe found that MODY3 participants had lower insulin secretion indices than controls and T2D participants, showing the expected β-cell defect. MODY3 had similar glycated hemoglobin levels (HbA1c median [IQR]: 6.5 [5.6–7.6]%) compared to T2D (median: 6.6 [6.2–6.9]%; P<0.05). MODY3 had greater insulin sensitivity (Matsuda index: 71.9 [29.6; 125.5]) than T2D (3.2 [4.0; 6.0]; P<0.05). MODY3 experienced a larger decrease in the ratio of NEFA to insulin (NEFA 30–0 / insulin 30–0: -39 [-78; -30] x104) in the early post-prandial period (0–30 minutes) compared to controls and to T2D (-2.0 [-0.6; -6.4] x104; P<0.05). MODY3 had lower fasting (0.66 [0.46; 1.2] mM) and post-meal triglycerides levels compared to T2D (fasting: 2.3 [1.7; 2.7] mM; P<0.05). We did not detect significant post-meal differences in ghrelin and incretins between MODY3 and other groups.ConclusionIn response to a standard meal test, MODY3 showed greater early post-prandial NEFA diminution in response to relatively low early insulin secretion, and they maintained very low post-prandial triglycerides levels.

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“…This result is not completely unprecedented: C10-modified ghrelin has occasionally been identified in non-mammalian vertebrates (14–17, 19, 21), and a C10-modified ghrelin is the major form in Mozambique tilapia (18). C10-modified ghrelin is also present in mammals (25, 26). In this study, we also detected ghrelin peptides acylated with C8, C9, and unsaturated decanoic acids (C10:1 and C10:2).…”

Section: Discussionmentioning

confidence: 99%

Determination of ghrelin structure in the barfin flounder (Verasper moseri) and involvement of ingested fatty acids in ghrelin acylation

et al. 2013

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Ghrelin is a peptide hormone that is acylated with a fatty acid, usually n-octanoic acid, at the third amino acid (aa) residue (usually a serine or threonine), and this acylation is known to be essential for ghrelin activity not only in mammals but also in non-mammals, such as fish. However, the modification mechanisms of ghrelin modification in fish are not known. In this study, we elucidated the structure of ghrelin in a teleost, the barfin flounder (Verasper moseri), and determined whether ingested free fatty acids of various chain lengths participated in ghrelin acylation. Complementary DNA cloning revealed the barfin flounder prepro-ghrelin to be a 106-aa peptide and the mature ghrelin to be a 20-aa peptide (GSSFLSPSHKPPNKGKPPRA). However, purification of ghrelin peptides from stomach extracts demonstrated that the major form of the hormone was a 19-aa decanoylated peptide [GSS(C10:0)FLSPSHKPPNKGKPPR] missing the last alanine of the 20-aa peptide. Ingestion of feed enriched with n-heptanoic acid (C7), n-octanoic acid (C8), or n-non-anoic acid (C9) changed the modification status of the peptide: ingestion of C8 or C9 increased the amount of C8:0 or C9:0 19-aa ghrelin, respectively, but no C7:0 ghrelin was isolated after ingestion of C7. These results indicate that ingested free fatty acids are substrates for ghrelin acylation in the barfin flounder, but the types of free fatty acids utilized as substrates may be limited.

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Plasma levels of n-decanoyl ghrelin, another acyl- and active-form of ghrelin, in human subjects and the effect of glucose- or meal-ingestion on its dynamics

Cited by 16 publications

References 50 publications

Changes in Subcellular Distribution of n-Octanoyl or n-Decanoyl Ghrelin in Ghrelin-Producing Cells

Changes in Subcellular Distribution of n-Octanoyl or n-Decanoyl Ghrelin in Ghrelin-Producing Cells

HNF1α defect influences post-prandial lipid regulation

Determination of ghrelin structure in the barfin flounder (Verasper moseri) and involvement of ingested fatty acids in ghrelin acylation

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