Abstract: The present invention provides a method to identify compounds useful in inhibiting the adverse effects of excessive FABP4 on the modulation of NDPK-ADK agonism of G protein-coupled receptors (GPCR) and channels in FABP4-mediated disorders. It has been surprisingly discovered that the fatty acid binding protein 4 (FABP4) inhibits the ability of the nucleoside diphosphate kinase (NDPK) and adenosine kinase (ADK) complex to agonize GPCRs on target cells by forming an NDPK-ADK/FABP4 complex, resulting in, amongst other things, impaired or reduced insulin secretion in islet ?-cells and an increase in glucose levels in the bloodstream. By inhibiting the formation of the NDPK-ADK/FABP4 complex, or inhibiting FABP4 downregulation of NDPK-ADK complex modulation of GPCRs, it has been discovered that FABP4-medited effects can be blunted, including the modulation of islet ?-cell insulin secretion, providing for a reduction in glucose levels and the attenuation of metabolic dysfunction.

Abstract: A method of predicting progression of gestational diabetes (GDM) to Type 2 diabetes (T2D) in a subject is provided. The method comprises: analyzing a biological sample of a subject to determine levels of a plurality of metabolites in the sample, wherein the plurality of metabolites comprises one or more of PCaeC40:5 and SM(OH)C14:1 and at least two metabolites set forth in Table 3, 4 and/or 6; and comparing the determined levels of the plurality of metabolites in the sample to a corresponding plurality of reference levels in order to predict progression of GDM to T2D in the subject.

Abstract: Provided are methods for identifying or monitoring a subject having, or at risk of developing, impaired glucose homeostasis. Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is shown to be a biomarker for impaired glucose homeostasis and/or conditions characterized by ?-cell dysfunction. Comparing a test level of CMPF in a subject to a control level identifies subjects having, or at risk of developing, impaired glucose homeostasis. Also provided are methods of causing impaired glucose homeostasis or ?-cell dysfunction and methods of screening for compounds that affect the activity of ?-cells. Also provided are methods for the treatment of ?-cell dysfunction by reducing the physiological levels of CMPF in a subject as well as the use of a OAT modulator for the treatment of ?-cell dysfunction.

Abstract: Provided are methods for identifying or monitoring a subject having, or at risk of developing, impaired glucose homeostasis. Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is shown to be a biomarker for impaired glucose homeostasis and/or conditions characterized by ?-cell dysfunction. Comparing a test level of CMPF in a subject to a control level identifies subjects having, or at risk of developing, impaired glucose homeostasis. Also provided are methods of causing impaired glucose homeostasis or ?-cell dysfunction and methods of screening for compounds that affect the activity of ?-cells. Also provided are methods for the treatment of ?-cell dysfunction by reducing the physiological levels of CMPF in a subject as well as the use of a OAT modulator for the treatment of ?-cell dysfunction.