Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents.

Scarlett JM, Rojas JM, Matsen ME, Kaiyala KJ, Stefanovski D, Bergman RN, Nguyen HT, Dorfman MD, Lantier L, Wasserman DH, Mirzadeh Z, Unterman TG, Morton GJ, Schwartz MW
Nat Med. 2016 22 (7): 800-6

PMID: 27213816 · PMCID: PMC4938755 · DOI:10.1038/nm.4101

Type 2 diabetes (T2D) is among the most common and costly disorders worldwide. The goal of current medical management for T2D is to transiently ameliorate hyperglycemia through daily dosing of one or more antidiabetic drugs. Hypoglycemia and weight gain are common side effects of therapy, and sustained disease remission is not obtainable with nonsurgical approaches. On the basis of the potent glucose-lowering response elicited by activation of brain fibroblast growth factor (FGF) receptors, we explored the antidiabetic efficacy of centrally administered FGF1, which, unlike other FGF peptides, activates all FGF receptor subtypes. We report that a single intracerebroventricular injection of FGF1 at a dose one-tenth of that needed for antidiabetic efficacy following peripheral injection induces sustained diabetes remission in both mouse and rat models of T2D. This antidiabetic effect is not secondary to weight loss, does not increase the risk of hypoglycemia, and involves a novel and incompletely understood mechanism for increasing glucose clearance from the bloodstream. We conclude that the brain has an inherent potential to induce diabetes remission and that brain FGF receptors are potential pharmacological targets for achieving this goal.

MeSH Terms (36)

Adipose Tissue Animals Blood Glucose Blotting, Western Body Composition Brain Carbon Radioisotopes Deoxyglucose Diabetes Mellitus, Experimental Diabetes Mellitus, Type 2 Diet, High-Fat Disease Models, Animal Ependymoglial Cells Fibroblast Growth Factor 1 Forkhead Box Protein O1 Glucose Tolerance Test Heart Heat-Shock Proteins Hyperglycemia Hypothalamus Injections, Intraventricular Liver Male Mice Mice, Knockout Mice, Obese Molecular Chaperones Muscle, Skeletal Myocardium Neoplasm Proteins Proto-Oncogene Proteins c-fos Rats Rats, Zucker Real-Time Polymerase Chain Reaction Receptor, Insulin Remission Induction

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