Fabkin and glucose homeostasis

Abstract

Background and aimsThe pathophysiology of different types of diabetes is incompletely understood. Fatty acid binding protein 4 (FABP4), an intracellular lipid chaperone, is secreted from adipocytes (during lipolysis) and macrophage. FABP4 is known to be associated with insulin resistance. However its precise role in the pathogenesis of T2DM is unclear. Fabkin, the hormonal complex of FABP4 with ADK (Adenosine Kinase) and NDPK (Nucleoside Diphosphate Kinase) is suggested to fill this gap in understanding pathogenesis. Herein, we summarize the role Fabkin in glucose homeostasis. MethodsPublished relevant manuscripts that discussed the effect of FABP4 and Fabkin on glucose homeostasis were reviewed. ResultsThe formation of Fabkin complex is driven by the strong affinities of FABP4 to ADK and to inherent high-affinity interaction of ADK with NDPK. It does not have any definite receptors. The complex acts through the following pathways: i) by modulation of Glucose-Stimulated Insulin Signalling (GSIS) through extracellular ADP/ATP interaction via G-protein-coupled purinergic P2Y1 receptors in pancreatic β-cells which are potently agonized by ADP and antagonized by ATP. Fabkin drives ADK to produce ATP, coupled with reduced generation of ADP. This results in low extracellular ADP/ATP ratio which leads to impairment of insulin secretion, ii) by regulating intracellular calcium dynamics iii) by producing Endoplasmic Reticulum (ER) stress. ConclusionsFabkin may integrate energy balance with functions of metabolic organs and thus play a major role in glucose homeostasis.