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Open AccessArticle

Circulating Levels of the Soluble Receptor for AGE (sRAGE) during Escalating Oral Glucose Dosages and Corresponding Isoglycaemic i.v. Glucose Infusions in Individuals with and without Type 2 Diabetes

1
Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia
2
School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, St Lucia, QLD 4072, Australia
3
Center for Clinical Metabolic Research, Herlev-Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark
4
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
5
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
6
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
7
Steno Diabetes Center Copenhagen, 2820 Gentofte, Denmark
8
Mater Clinical School, Faculty of Medicine, The University of Queensland, South Brisbane, QLD 4101, Australia
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(10), 2928; https://doi.org/10.3390/nu12102928
Received: 15 July 2020 / Revised: 11 September 2020 / Accepted: 21 September 2020 / Published: 24 September 2020
(This article belongs to the Special Issue Carbohydrates, Metabolism and Therapies in Diabetes)
Postprandial glucose excursions are postulated to increase the risk for diabetes complications via the production of advanced glycation end products (AGEs). The soluble receptor of AGEs (sRAGE) likely acts as a decoy receptor, mopping up AGEs, diminishing their capacity for pro-inflammatory and pro-apoptotic signaling. Recent evidence suggests that AGEs and soluble receptor for AGEs (sRAGE) may be altered under postprandial and fasting conditions. Here, we investigated the effects of increasing oral glucose loads during oral glucose tolerance tests (OGTT) and matched isoglycaemic intravenous (i.v.) glucose infusions (IIGI) on circulating concentrations of sRAGE. Samples from eight individuals with type 2 diabetes and eight age-, gender-, and body mass index (BMI)-matched controls, all of whom underwent three differently dosed OGTTs (25 g, 75 g, and 125 g), and three matched IIGIs were utilised (NCT00529048). Serum concentrations of sRAGE were measured over 240 min during each test. For individuals with diabetes, sRAGE area under the curve (AUC0–240min) declined with increasing i.v. glucose dosages (p < 0.0001 for trend) and was lower during IIGI compared to OGTT at the 125 g dosage (p = 0.004). In control subjects, sRAGE AUC0–240min was only lower during IIGI compared to OGTT at the 25 g dose (p = 0.0015). sRAGE AUC0–240min was negatively correlated to AUC0–240min for the incretin hormone glucagon-like peptide −1 (GLP-1) during the 75 g OGTT and matched IIGI, but only in individuals with type 2 diabetes. These data suggest that gastrointestinal factors may play a role in regulating sRAGE concentrations during postprandial glucose excursions, thus warranting further investigation. View Full-Text
Keywords: RAGE; sRAGE; AGEs; type 2 diabetes mellitus; diabetes complications; metabolic alterations of T2DM; enteroendocrine RAGE; sRAGE; AGEs; type 2 diabetes mellitus; diabetes complications; metabolic alterations of T2DM; enteroendocrine
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MDPI and ACS Style

Fotheringham, A.K.; Bagger, J.I.; Borg, D.J.; McCarthy, D.A.; Holst, J.J.; Vilsbøll, T.; Knop, F.K.; Forbes, J.M. Circulating Levels of the Soluble Receptor for AGE (sRAGE) during Escalating Oral Glucose Dosages and Corresponding Isoglycaemic i.v. Glucose Infusions in Individuals with and without Type 2 Diabetes. Nutrients 2020, 12, 2928. https://doi.org/10.3390/nu12102928

AMA Style

Fotheringham AK, Bagger JI, Borg DJ, McCarthy DA, Holst JJ, Vilsbøll T, Knop FK, Forbes JM. Circulating Levels of the Soluble Receptor for AGE (sRAGE) during Escalating Oral Glucose Dosages and Corresponding Isoglycaemic i.v. Glucose Infusions in Individuals with and without Type 2 Diabetes. Nutrients. 2020; 12(10):2928. https://doi.org/10.3390/nu12102928

Chicago/Turabian Style

Fotheringham, Amelia K.; Bagger, Jonatan I.; Borg, Danielle J.; McCarthy, Domenica A.; Holst, Jens J.; Vilsbøll, Tina; Knop, Filip K.; Forbes, Josephine M. 2020. "Circulating Levels of the Soluble Receptor for AGE (sRAGE) during Escalating Oral Glucose Dosages and Corresponding Isoglycaemic i.v. Glucose Infusions in Individuals with and without Type 2 Diabetes" Nutrients 12, no. 10: 2928. https://doi.org/10.3390/nu12102928

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