Xin Yan1, Zhen Wang1, Sidse Westberg-Rasmussen2, Marcel Tarbier3, Thomas Rathjen1, Sudhir G Tattikota1, Bailey C E Peck4, Matt Kanke5, Claus Oxvig6, Jan Frystyk7, Jakob Starup-Linde2, Praveen Sethupathy5, Marc R Friedländer3, Søren Gregersen2, Matthew N Poy1. 1. Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany. 2. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, DK-8000 Aarhus, Denmark. 3. Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 17121 Stockholm, Sweden. 4. Department of Surgery, School of Medicine, University of Michigan, Ann Arbor, Michigan 48109. 5. Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853. 6. Department of Molecular Biology and Genetics, Science and Technology, Aarhus University, DK-8000 Aarhus, Denmark. 7. Medical Research Laboratory, Department of Clinical Medicine, Health, Aarhus University, DK-8000 Aarhus, Denmark.
Abstract
Background: To date, numerous nucleic acid species have been detected in the systemic circulation including microRNAs (miRNAs); however, their functional role in this compartment remains unclear. Objective: The aim of this study was to determine whether systemic levels of miRNAs abundant in blood, including the neuroendocrine tissue-enriched miR-375, are altered in response to a glucose challenge. Design: Twelve healthy males were recruited for an acute crossover study that consisted of two tests each following an 8-hour fasting period. An oral glucose tolerance test (OGTT) was performed, and blood samples were collected over a 3-hour period. Following a period of at least 1 week, the same participants were administered an isoglycemic intravenous glucose infusion (IIGI) with the same blood-collection protocol. Results: The glucose response curve following the IIGI mimicked that obtained after the OGTT, but as expected, systemic insulin levels were lower during the IIGI compared with the OGTT (P < 0.05). miR-375 levels in circulation were increased only in response to an OGTT and not during an IIGI. In addition, the response to the OGTT also coincided with the transient increase of circulating glucagon-like peptide (GLP)-1, GLP-2, and glucose-dependent insulinotropic polypeptide. Conclusions: The present findings show levels of miR-375 increase following administration of an OGTT and, in light of its enrichment in cells of the gut, suggest that the gastrointestinal tract may play an important role in the abundance and function of this miRNA in the blood.
Background: To date, numerous nucleic acid species have been detected in the systemic circulation including microRNAs (miRNAs); however, their functional role in this compartment remains unclear. Objective: The aim of this study was to determine whether systemic levels of miRNAs abundant in blood, including the neuroendocrine tissue-enriched miR-375, are altered in response to a glucose challenge. Design: Twelve healthy males were recruited for an acute crossover study that consisted of two tests each following an 8-hour fasting period. An oral glucose tolerance test (OGTT) was performed, and blood samples were collected over a 3-hour period. Following a period of at least 1 week, the same participants were administered an isoglycemic intravenous glucose infusion (IIGI) with the same blood-collection protocol. Results: The glucose response curve following the IIGI mimicked that obtained after the OGTT, but as expected, systemic insulin levels were lower during the IIGI compared with the OGTT (P < 0.05). miR-375 levels in circulation were increased only in response to an OGTT and not during an IIGI. In addition, the response to the OGTT also coincided with the transient increase of circulating glucagon-like peptide (GLP)-1, GLP-2, and glucose-dependent insulinotropic polypeptide. Conclusions: The present findings show levels of miR-375 increase following administration of an OGTT and, in light of its enrichment in cells of the gut, suggest that the gastrointestinal tract may play an important role in the abundance and function of this miRNA in the blood.