Mass spectrometric characterisation of the circulating peptidome following oral glucose ingestion in control and gastrectomised patients

Kay, Richard G.; Foreman, Rachel E.; Roberts, Geoffrey; Hardwick, Richard; Reimann, Frank; Gribble, Fiona M.

doi:10.1101/2020.03.23.002899

Cited by 3 publications

(3 citation statements)

References 27 publications

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“…At these heightened concentrations, untargeted approaches can detect and quantify them to compare plasma levels during an oral glucose tolerance test. 126…”

Section: Diabetes and Gut Hormonesmentioning

confidence: 99%

Peptidomics: A Review of Clinical Applications and Methodologies

et al. 2021

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Improvements in both liquid chromatography (LC) and mass spectrometry (MS) instrumentation have greatly enhanced proteomic and small molecule metabolomic analysis in recent years. Less focus has been on the improved capability to detect and quantify small bioactive peptides, even though the exact sequences of the peptide species produced can have important biological consequences. Endogenous bioactive peptide hormones, for example, are generated by the targeted and regulated cleavage of peptides from their prohormone sequence. This process may include organ specific variants, as proglucagon is converted to glucagon in the pancreas but glucagon-like peptide-1 (GLP-1) in the small intestine, with glucagon raising, whereas GLP-1, as an incretin, lowering blood glucose. Therefore, peptidomics workflows must preserve the structure of the processed peptide products to prevent the misidentification of ambiguous peptide species. The poor in vivo and in vitro stability of peptides in biological matrices is a major factor that needs to be considered when developing methods to study them. The bioinformatic analysis of peptidomics data sets requires the inclusion of specific posttranslational modifications, which are critical for the function of many bioactive peptides. This review aims to discuss and contrast the various extraction, analytical, and bioinformatics approaches used for human peptidomics studies in a multitude of matrices.

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“…At these heightened concentrations, untargeted approaches can detect and quantify them to compare plasma levels during an oral glucose tolerance test. 126…”

Section: Diabetes and Gut Hormonesmentioning

confidence: 99%

Peptidomics: A Review of Clinical Applications and Methodologies

et al. 2021

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“…A study of healthy volunteers found that consumption of a meal with a high glycemic index was associated with a blunted release of motilin compared to a meal with a low glycemic index [124]. Similarly, the consumption of glucose in diabetic patients undergoing a glucose tolerance test resulted in a significant decrease in plasma motilin [125]. In contrast, the administration of prebiotics resulted in increases in motilin levels in an animal model of constipation [126].…”

Section: Conceptual Analysis Of the Links Between Motilin And Depressionmentioning

confidence: 99%

Gut Hormones as Potential Therapeutic Targets or Biomarkers of Response in Depression: The Case of Motilin

Rajkumar¹

2021

Preprint

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Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (a) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, and (b) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression. It was observed that (a) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (b) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required, and that these molecular pathways represent potential future mechanisms for antidepressant drug development.

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“…As this bioanalytical technique is readily multiplexable, it was simultaneously developed for the comeasurement of insulin, C-peptide, GIP (1-42) and GIP . Bioactive GIP(1-42) only circulates for a short time before inactivation by dipeptidyl peptidase IV to produce inactive GIP (3-42) (19); the use of targeted LC-MS/MS provides the opportunity to quantify both GIP isoforms simultaneously due to their difference in molecular weight, as described in previous LC-MS/ MS protocols (20)(21)(22). Immunoassay analysis was additionally performed for active ghrelin and total GIP, to correlate ghrelin and motilin profiles, and compare the different methods for GIP detection.…”

Section: Introductionmentioning

confidence: 99%

Motilin fluctuations in healthy volunteers determined by liquid chromatography mass spectrometry

Foreman,

Bannon,

Kay

et al. 2024

Front. Endocrinol.

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IntroductionMotilin is a hormone secreted by specialised enteroendocrine cells in the small intestine, and is known to modulate gastrointestinal motility in humans, regulating the migratory motor complex. It is understudied at least in part due to the lack of commercially available immunoassays.MethodA multiplexed liquid chromatography mass spectrometry (LC-MS/MS) method was optimised to measure motilin, insulin, C-peptide, GIP (1–42) and GIP (3–42). Corresponding active ghrelin concentrations were determined by immunoassay. Ten healthy volunteers with no prior history of gastroenterological or endocrine condition attended after overnight fast and had blood samples taken every 15 minutes for 4 hours whilst continuing to fast, and then further sampling for 2 hours following a liquid mixed meal. Hunger scores were taken at each time point using a visual analogue scale. Normal bowel habit was confirmed by 1 week stool diary.ResultsMotilin levels fluctuated in the fasting state with an average period between peaks of 109.5 mins (SD:30.0), but with no evidence of a relationship with either ghrelin levels or hunger scores. The mixed meal interrupted cyclical motilin fluctuations, increased concentrations of motilin, insulin, C-peptide, GIP(1-42) and GIP(3-42), and suppressed ghrelin levels.DiscussionThis study highlights the utility of LC-MS/MS for parallel measurement of motilin alongside other peptide hormones, and supports previous reports of the cyclical nature of motilin levels in the fasting state and interruption with feeding. This analytical method has utility for further clinical studies into motilin and gut hormone physiology in human volunteers.

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Mass spectrometric characterisation of the circulating peptidome following oral glucose ingestion in control and gastrectomised patients

Cited by 3 publications

References 27 publications

Peptidomics: A Review of Clinical Applications and Methodologies

Peptidomics: A Review of Clinical Applications and Methodologies

Gut Hormones as Potential Therapeutic Targets or Biomarkers of Response in Depression: The Case of Motilin

Motilin fluctuations in healthy volunteers determined by liquid chromatography mass spectrometry

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