Metabolic and proteomic signatures of hypoglycaemia in type 2 diabetes.
Adult
Amino Acids
/ metabolism
Bile Acids and Salts
/ metabolism
Blood Glucose
/ metabolism
Case-Control Studies
Diabetes Mellitus, Type 2
/ metabolism
Fatty Acids
/ metabolism
Female
Glucose Clamp Technique
Healthy Volunteers
Humans
Hypoglycemia
/ metabolism
Inflammation
/ metabolism
Lipid Metabolism
Male
Metabolomics
Middle Aged
Proteomics
Steroids
/ metabolism
clinical physiology
glucose metabolism
hypoglycaemia
type 2 diabetes
Journal
Diabetes, obesity & metabolism
ISSN: 1463-1326
Titre abrégé: Diabetes Obes Metab
Pays: England
ID NLM: 100883645
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
03
09
2018
revised:
20
11
2018
accepted:
01
12
2018
pubmed:
14
12
2018
medline:
8
9
2020
entrez:
8
12
2018
Statut:
ppublish
Résumé
To determine the biochemical changes that underlie hypoglycaemia in a healthy control group and in people with type 2 diabetes (T2D). We report a hypoglycaemic clamp study in seven healthy controls and 10 people with T2D. Blood was withdrawn at four time points: at baseline after an overnight fast; after clamping to euglycaemia at 5 mmol/L; after clamping to hypoglycaemia at 2.8 mmol/L; and 24 hours later, after overnight fast. Deep molecular phenotyping using non-targeted metabolomics and the SomaLogic aptamer-based proteomics platform was performed on collected samples. A total of 955 metabolites and 1125 proteins were identified, with significant alterations in >90 molecules. A number of metabolites significantly increased during hypoglycaemia, but only cortisol, adenosine-3',5'-cyclic monophosphate (cyclic AMP), and pregnenolone sulphate, were independent of insulin. By contrast, identified protein changes were triggered by hypoglycaemia rather than insulin. The T2D group had significantly higher levels of fatty acids including 10-nonadecenoate, linolenate and dihomo-linoleate during hypoglycaemia compared with the control group. Molecules contributing to cardiovascular complications such as fatty-acid-binding protein-3 and pregnenolone sulphate were altered in the participants with T2D during hypoglycaemia. Almost all molecules returned to baseline at 24 hours. The present study provides a comprehensive description of molecular events that are triggered by insulin-induced hypoglycaemia. We identified deregulated pathways in T2D that may play a role in the pathophysiology of hypoglycaemia-induced cardiovascular complications.
Substances chimiques
Amino Acids
0
Bile Acids and Salts
0
Blood Glucose
0
Fatty Acids
0
Steroids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
909-919Informations de copyright
© 2018 John Wiley & Sons Ltd.
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