Differential impact of glucose administered intravenously and orally on circulating mir-375 levels in human subjects


  • X. Yan
  • Z. Wang
  • S. Westberg-Rasmussen
  • M. Tarbier
  • T. Rathjen
  • S.G. Tattikota
  • B.C.E. Peck
  • M. Kanke
  • C. Oxvig
  • J. Frystyk
  • J. Starup-Linde
  • P. Sethupathy
  • M.R. Friedlaender
  • S. Gregersen
  • M.N. Poy


  • Journal of Clinical Endocrinology and Metabolism


  • J Clin Endocrinol Metab 102 (10): 3749-3755


  • 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 cross-over study which consisted of two tests each following an eight-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 one 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 to 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-1 (GLP-1), glucagon-like peptide-2 (GLP-2), and glucose-dependent insulinotropic polypeptide (GIP). 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 a significant role to the abundance and function of this microRNA in the blood.