title: Fibroblast growth factors: new insights, new targets in the management of diabetes.
abstract: The fibroblast growth factor (FGF) family consists of 22 evolutionarily and structurally related proteins (FGF1 to FGF23; with FGF15 being the rodent ortholog of human FGF19). Based on their mechanism of action, FGFs can be categorized into intracrine, autocrine/paracrine and endocrine subgroups. Both autocrine/paracrine and endocrine FGFs are secreted from their cells of origin and exert their effects on target cells by binding to and activating specific single-pass transmembrane tyrosine kinase receptors (FGFRs). Moreover, FGF binding to FGFRs requires specific cofactors, namely heparin/heparan sulfate proteoglycans or Klothos for autocrine/paracrine and endocrine FGF signaling, respectively. FGFs are vital for embryonic development and mediate a broad spectrum of biological functions, ranging from cellular excitability to angiogenesis and tissue regeneration. Over the past decade certain FGFs (e.g. FGF1, FGF10, FGF15/FGF19 and FGF21) have been further recognized as regulators of energy homeostasis, metabolism and adipogenesis, constituting novel therapeutic targets for obesity and obesity-related cardiometabolic disease. Until recently, translational research has been mainly focused on FGF21, due to the pleiotropic, beneficial metabolic actions and the relatively benign safety profile of its engineered variants. However, increasing evidence regarding the role of additional FGFs in the regulation of metabolic homeostasis and recent developments regarding novel, engineered FGF variants have revitalized the research interest into the therapeutic potential of certain additional FGFs (e.g. FGF1 and FGF15/FGF19). This review presents a brief overview of the FGF family, describing the mode of action of the different FGFs subgroups, and focuses on FGF1 and FGF15/FGF19, which appear to also represent promising new targets for the treatment of obesity and type 2 diabetes.
authors.affiliation: Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, UK.|Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.|Warwick Medical School, University of Warwick, Coventry, UK.|Centre of Applied Biological and Exercise Sciences (ABES), Faculty of Health and Life Sciences, Coventry University, Coventry, UK.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kyrou
authors.affiliation: Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.|Warwick Medical School, University of Warwick, Coventry, UK.|Centre of Applied Biological and Exercise Sciences (ABES), Faculty of Health and Life Sciences, Coventry University, Coventry, UK.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Weickert
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Seley
authors.initials: S
authors.lastname: Gharanei
authors.affiliation: Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, UK.|Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.|Warwick Medical School, University of Warwick, Coventry, UK.|Centre of Applied Biological and Exercise Sciences (ABES), Faculty of Health and Life Sciences, Coventry University, Coventry, UK.
authors.forename: Harpal S
authors.initials: HS
authors.lastname: Randeva
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK - b.k.tan@warwick.ac.uk.|Birmingham Heartlands Hospital, Heart of England NHS Foundation NHS Trust, Birmingham, UK.
authors.forename: Bee K
authors.initials: BK
authors.lastname: Tan
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy
chemical_list: C000717427:FGF23 protein, human; D007004:Hypoglycemic Agents; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23