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Synthesis and Characterization of Urofuranoic Acids: In Vivo Metabolism of 2‑(2-Carboxyethyl)-4-methyl-5-propylfuran-3-carboxylic Acid (CMPF) and Effects on in Vitro Insulin Secretion

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posted on 07.02.2017, 00:00 authored by Edith Nagy, Ying Liu, Kacey J. Prentice, Kyle W. Sloop, Phillip E. Sanders, Battsetseg Batchuluun, Craig D. Hammond, Michael B. Wheeler, Timothy B. Durham
CMPF (2-(2-carboxyethyl)-4-methyl-5-propylfuran-3-carboxylic acid) is a metabolite that circulates at high concentrations in type 2 and gestational diabetes patients. Further, human clinical studies suggest it might have a causal role in these diseases. CMPF inhibits insulin secretion in mouse and human islets in vitro and in vivo in rodents. However, the metabolic fate of CMPF and the relationship of structure to effects on insulin secretion have not been significantly studied. The syntheses of CMPF and analogues are described. These include isotopically labeled molecules. Study of these materials in vivo has led to the first observation of a metabolite of CMPF. In addition, a wide range of CMPF analogues have been prepared and characterized in insulin secretion assays using both mouse and human islets. Several molecules that influence insulin secretion in vitro were identified. The molecules described should serve as interesting probes to further study the biology of CMPF.