Implications of Fibroblast growth factor/Klotho system in glucose metabolism and diabetes

• Fibroblast growth factors (FGF)/Klotho system is a new biological system with relevant metabolic implications.
• Endocrine FGF participate in glucose metabolism (hepatic glucose synthesis, glucose uptake, insulin sensitivity, etc.).
• Moreover, these factors have been related to the pathophysiology of diabetes mellitus.
• In addition, they can offer new potential therapeutic targets for treatment of diabetes.

ABSTRACTDiabetes mellitus, especially type 2 diabetes, remains the dominant metabolic disease worldwide, with an expected increase in prevalence of over 50% in the next 20 years. Our knowledge about the pathophysiology of type 2 diabetes continues to be incomplete, with unmet medical need for new therapies. The characterization of the fibroblast growth factor (FGF) family and the discovery of endocrine FGFs provided new information on the mechanisms of regulation and homeostasis of carbohydrate metabolism. More specifically, FGF19 and FGF21 signaling pathways have been linked to different glucose metabolic processes, including hepatic glucose synthesis, glycogen synthesis, glucose uptake, and insulin sensitivity, among others, and these molecules have been further related to the pathophysiology of diabetes mellitus. In-depth comprehension of these growth factors may bring to light new potential therapeutic targets for the treatment of diabetes mellitus.