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Metabolomics and flux analysis by mass spectrometry : Investigations of factors associated with insulin secretion and prostate cancer risk

Östman, Johnny (2021). Metabolomics and flux analysis by mass spectrometry : Investigations of factors associated with insulin secretion and prostate cancer risk. Diss. (sammanfattning/summary) Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae, 1652-6880
ISBN 978-91-7760-714-4
eISBN 978-91-7760-715-1
[Doctoral thesis]

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Abstract

Two of the most common diseases associated with the Western lifestyle are type 2 diabetes (T2D) and prostate cancer (PCa). This is in large part due to decreased physical activity, surplus of dietary energy, and an ageing population. T2D and PCa are illnesses that develop during a long period of time and metabolic alterations associated with the diseases are not known in detail. Three studies investigating metabolic alterations associated with the risk of T2D and PCa were performed using liquid chromatography-high-resolution mass spectrometry-based metabolomics and stable isotope labelling.

A human intervention study investigating insulin secretion in response to breads varying in digestibility showed a decreased insulin response when rye bread was ingested in comparison with wheat bread, owing to a reduced rate of glucose appearance in blood, even though the blood glucose levels were unaffected.

Short-term incubation of human EndoC-βH1 cells with glucose and/or palmitic acid in vitro showed an increased Krebs cycle activity by glucose and an increased Krebs cycle flux by palmitate co-incubation, possibly mediated via pyruvate carboxylase. Proline containing carbon from the added glucose was also formed and excreted by the cells, uncovering a new fuel excess detoxification process.

An untargeted metabolomics study using 752 case-control pairs of fasting plasma samples matched by age, BMI, and sample storage time from the Northern Sweden Health and Disease Study was conducted in order to look for metabolites prospectively associated with prostate cancer risk. This is the largest prospective untargeted metabolomics study focused on PCa risk to date. Metabolites belonging to different chemical classes i.a. aromatic amino acids, several kinds of phospholipids, and free fatty acids were found to be positively associated with the risk of future PCa, while glucose was found to be inversely associated. Stratification by disease aggressiveness and by baseline age showed variations in which metabolites were associated with PCa risk, as well as showing variations in their degrees of association.

Authors/Creators:Östman, Johnny
Title:Metabolomics and flux analysis by mass spectrometry : Investigations of factors associated with insulin secretion and prostate cancer risk
Series Name/Journal:Acta Universitatis Agriculturae Sueciae
Year of publishing :2021
Number:2021:18
Number of Pages:158
Publisher:Department of Molecular Sciences, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-7760-714-4
ISBN for electronic version:978-91-7760-715-1
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Article category:Other scientific
Version:Published version
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 104 Chemical Sciences > Analytical Chemistry
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Biochemistry and Molecular Biology
Keywords:Metabolomics, metabolic flux, LC-MS, liquid chromatography, mass spectrometry, stable isotopes, type 2 diabetes, prostate cancer, β-cells, NSHDS
URN:NBN:urn:nbn:se:slu:epsilon-p-110867
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-110867
ID Code:22691
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(NL, NJ) > Department of Molecular Sciences
Deposited By: SLUpub Connector
Deposited On:03 Mar 2021 08:28
Metadata Last Modified:03 Mar 2021 14:00

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