title: Fibroblast growth factor 21 analogue LY2405319 lowers blood glucose in streptozotocin-induced insulin-deficient diabetic mice by restoring brown adipose tissue function.
abstract: OBJECTIVE
  To investigate the effects of LY2405319, an analogue of fibroblast growth factor 21 (FGF21), on glucose homeostasis in streptozotocin (STZ)-induced insulin-deficient mice (STZ mice).
  
  
  METHODS
  Nine-week-old male C57BL/6J mice were administered a single intraperitoneal injection of STZ (150 mg/kg). One week later, after confirmation of hyperglycaemia, saline or LY2405319 (5 mg/kg) was injected subcutaneously daily for 4 weeks. Changes in glucose homeostasis, energy metabolism and brown adipose tissue (BAT) function were assessed.
  
  
  RESULTS
  The STZ mice had elevated blood glucose and reduced plasma FGF21 levels, impaired glucose uptake in the BAT, and BAT mitochondria with absent or swollen cristae and fewer lipid vacuoles. LY2405319 significantly reduced blood glucose levels and this was associated with increased BAT glucose uptake and changes in gene expression and morphology, indicating improved mitochondrial lipid metabolism in the BAT. Importantly, the ability of LY2405319 to lower blood glucose in STZ mice was compromised after removing interscapular BAT.
  
  
  CONCLUSIONS
  Our results show that LY2405319 reduces blood glucose levels in insulin-deficient diabetes by improving BAT metabolism. Additional studies investigating the therapeutic potential of FGF21 for the treatment of type 1 diabetes are warranted.
authors.affiliation: Department of Biomedical Science, Graduate school of Medicine, Kyungpook National University, Daegu, South Korea; Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu, South Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.forename: K-H
authors.initials: KH
authors.lastname: Bae
authors.forename: Y-K
authors.initials: YK
authors.lastname: Choi
authors.forename: Y
authors.initials: Y
authors.lastname: Go
authors.forename: M
authors.initials: M
authors.lastname: Choe
authors.forename: Y-H
authors.initials: YH
authors.lastname: Jeon
authors.forename: H-W
authors.initials: HW
authors.lastname: Lee
authors.forename: S-H
authors.initials: SH
authors.lastname: Koo
authors.forename: J W
authors.initials: JW
authors.lastname: Perfield
authors.forename: R A
authors.initials: RA
authors.lastname: Harris
authors.forename: I-K
authors.initials: IK
authors.lastname: Lee
authors.forename: K-G
authors.initials: KG
authors.lastname: Park
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000503:physiopathology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006706:Homeostasis; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000172:deficiency; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D007328:Insulin; C585266:LY2405319; C414620:fibroblast growth factor 21; D013311:Streptozocin; D005346:Fibroblast Growth Factors
keywords: antidiabetic drug; glucose uptake; type 1 diabetes