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
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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. / Fotheringham, Amelia K.; Bagger, Jonatan I.; Borg, Danielle J.; McCarthy, Domenica A.; Holst, Jens J.; Vilsbøll, Tina; Knop, Filip K.; Forbes, Josephine M.
In: Nutrients, Vol. 12, No. 10, 2928, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - 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
AU - Fotheringham, Amelia K.
AU - Bagger, Jonatan I.
AU - Borg, Danielle J.
AU - McCarthy, Domenica A.
AU - Holst, Jens J.
AU - Vilsbøll, Tina
AU - Knop, Filip K.
AU - Forbes, Josephine M.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - AGEs
KW - diabetes complications
KW - enteroendocrine
KW - metabolic alterations of T2DM
KW - RAGE
KW - sRAGE
KW - type 2 diabetes mellitus
U2 - 10.3390/nu12102928
DO - 10.3390/nu12102928
M3 - Journal article
C2 - 32987824
AN - SCOPUS:85092070324
VL - 12
JO - Nutrients
JF - Nutrients
SN - 2072-6643
IS - 10
M1 - 2928
ER -
ID: 250385815