Fibroblast growth factor 21 analogue LY2405319 lowers blood glucose in streptozotocin‐induced insulin‐deficient diabetic mice by restoring brown adipose tissue function. Issue 2 (28th November 2014)

• Record Type: Journal Article
• Authors: Kim, J.‐H.; Bae, K.‐H.; Choi, Y.‐K.; Go, Y.; Choe, M.; Jeon, Y.‐H.; Lee, H.‐W.; Koo, S.‐H.; Perfield, J. W.; Harris, R. A.; Lee, I.‐K.; Park, K.‐G.
• Is Part Of: Diabetes, obesity & metabolism. Volume 17:Issue 2(2015:Feb.)
• Page Start: 161
• Page End: 169
• Publication Date: 2014-11-28
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12408
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main" id="dom12408-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="dom12408-sec-0001" sec-type="section"> <title>Aim</title> <p id="dom12408-para-0001">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).</p> </sec> <sec id="dom12408-sec-0002" sec-type="section"> <title>Methods</title> <p id="dom12408-para-0002">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.</p> </sec> <sec id="dom12408-sec-0003" sec-type="section"> <title>Results</title> <p id="dom12408-para-0003">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.</p> </sec> <sec id="dom12408-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="dom12408-para-0004">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.</p> </sec> </abstract>