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Fibroblast growth factor 21 prevents glycemic deterioration in insulin deficient mouse models of diabetes.

Andersen, Birgitte; Omar, Bilal LU ; Rakipovski, Günaj; Raun, Kirsten and Ahrén, Bo LU (2015) In European Journal of Pharmacology 764. p.189-194
Abstract
In type 1 diabetes, there is a rapid loss of glycemic control immediately after onset of the disease. We aimed to determine if the deterioration of glycemic control that occurs early after the onset of insulin-deficient diabetes could be blunted by treatment with recombinant fibroblast growth factor 21 (FGF21). Normal C57BL/6J mice made diabetic by a single high dose injection of streptozotocin (STZ) were randomized to receive twice daily subcutaneous injection of vehicle or recombinant human FGF21 at doses of 0.3 and 1.0mg/kg for 10 days. Body weight was recorded daily and 5h fasted glucose, insulin, glucagon, free fatty acids and ketones were determined at 6 and 10 days post-randomization. The increase in fasting plasma glucose induced... (More)
In type 1 diabetes, there is a rapid loss of glycemic control immediately after onset of the disease. We aimed to determine if the deterioration of glycemic control that occurs early after the onset of insulin-deficient diabetes could be blunted by treatment with recombinant fibroblast growth factor 21 (FGF21). Normal C57BL/6J mice made diabetic by a single high dose injection of streptozotocin (STZ) were randomized to receive twice daily subcutaneous injection of vehicle or recombinant human FGF21 at doses of 0.3 and 1.0mg/kg for 10 days. Body weight was recorded daily and 5h fasted glucose, insulin, glucagon, free fatty acids and ketones were determined at 6 and 10 days post-randomization. The increase in fasting plasma glucose induced by STZ in untreated mice was prevented with FGF21 at 0.3mg/kg BID. In contrast, at 1.0mg/kg BID, FGF21 did not prevent the rise in plasma glucose after STZ. At the end of the study, plasma glucagon was significantly higher in the diabetic group treated with FGF21 1.0mg/kg BID than in the untreated group. This was not seen for the group treated with FGF21 0.3mg/kg BID. There were significant dose dependent reductions in plasma free fatty acids with FGF21 treatment but no significant change in plasma ketones (β-hydroxybutyrate). FGF21 treatment did not have significant effects on body weight in lean insulin deficient mice. In conclusion, FGF21 prevents increases in glycaemia and has lipid lowering properties in mouse models of insulin deficient diabetes, although by increasing the dose increased glucagon levels are seen and hyperglycemia persists. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmacology
volume
764
pages
189 - 194
publisher
Elsevier
external identifiers
  • pmid:26144370
  • wos:000362987800023
  • scopus:84936851485
ISSN
1879-0712
DOI
10.1016/j.ejphar.2015.07.003
language
English
LU publication?
yes
id
76bc761b-08fa-467d-b4f2-99098efd13e8 (old id 7750690)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26144370?dopt=Abstract
date added to LUP
2015-08-06 22:24:45
date last changed
2017-11-19 03:21:48
@article{76bc761b-08fa-467d-b4f2-99098efd13e8,
  abstract     = {In type 1 diabetes, there is a rapid loss of glycemic control immediately after onset of the disease. We aimed to determine if the deterioration of glycemic control that occurs early after the onset of insulin-deficient diabetes could be blunted by treatment with recombinant fibroblast growth factor 21 (FGF21). Normal C57BL/6J mice made diabetic by a single high dose injection of streptozotocin (STZ) were randomized to receive twice daily subcutaneous injection of vehicle or recombinant human FGF21 at doses of 0.3 and 1.0mg/kg for 10 days. Body weight was recorded daily and 5h fasted glucose, insulin, glucagon, free fatty acids and ketones were determined at 6 and 10 days post-randomization. The increase in fasting plasma glucose induced by STZ in untreated mice was prevented with FGF21 at 0.3mg/kg BID. In contrast, at 1.0mg/kg BID, FGF21 did not prevent the rise in plasma glucose after STZ. At the end of the study, plasma glucagon was significantly higher in the diabetic group treated with FGF21 1.0mg/kg BID than in the untreated group. This was not seen for the group treated with FGF21 0.3mg/kg BID. There were significant dose dependent reductions in plasma free fatty acids with FGF21 treatment but no significant change in plasma ketones (β-hydroxybutyrate). FGF21 treatment did not have significant effects on body weight in lean insulin deficient mice. In conclusion, FGF21 prevents increases in glycaemia and has lipid lowering properties in mouse models of insulin deficient diabetes, although by increasing the dose increased glucagon levels are seen and hyperglycemia persists.},
  author       = {Andersen, Birgitte and Omar, Bilal and Rakipovski, Günaj and Raun, Kirsten and Ahrén, Bo},
  issn         = {1879-0712},
  language     = {eng},
  pages        = {189--194},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Fibroblast growth factor 21 prevents glycemic deterioration in insulin deficient mouse models of diabetes.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2015.07.003},
  volume       = {764},
  year         = {2015},
}