[HTML][HTML] The human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and …

M Shimoda, Y Kanda, S Hamamoto, K Tawaramoto… - Diabetologia, 2011 - Springer
M Shimoda, Y Kanda, S Hamamoto, K Tawaramoto, M Hashiramoto, M Matsuki, K Kaku
Diabetologia, 2011Springer
Aims/hypothesis We investigated the molecular mechanism by which the human glucagon-
like peptide-1 analogue liraglutide preserves pancreatic beta cells in diabetic db/db mice.
Methods Male db/db and m/m mice aged 10 weeks received liraglutide or vehicle for 2 days
or 2 weeks. In addition to morphological and biochemical analysis of pancreatic islets, gene
expression profiles in the islet core area were investigated by laser capture microdissection
and real-time RT-PCR. Results Liraglutide treatment for 2 weeks improved metabolic …
Aims/hypothesis
We investigated the molecular mechanism by which the human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells in diabetic db/db mice.
Methods
Male db/db and m/m mice aged 10 weeks received liraglutide or vehicle for 2 days or 2 weeks. In addition to morphological and biochemical analysis of pancreatic islets, gene expression profiles in the islet core area were investigated by laser capture microdissection and real-time RT-PCR.
Results
Liraglutide treatment for 2 weeks improved metabolic variables and insulin sensitivity in db/db mice. Liraglutide also increased glucose-stimulated insulin secretion (GSIS) and islet insulin content in both mouse strains and reduced triacylglycerol content in db/db mice. Expression of genes involved in cell differentiation and proliferation in both mouse strains was regulated by liraglutide, which, in db/db mice, downregulated genes involved in pro-apoptosis, endoplasmic reticulum (ER) stress and lipid synthesis, and upregulated genes related to anti-apoptosis and anti-oxidative stress. In the 2 day experiment, liraglutide slightly improved metabolic variables in db/db mice, but GSIS, insulin and triacylglycerol content were not affected. In db/db mice, liraglutide increased gene expression associated with cell differentiation, proliferation and anti-apoptosis, and suppressed gene expression involved in pro-apoptosis; it had no effect on genes related to oxidative stress or ER stress. Morphometric results for cell proliferation, cell apoptosis and oxidative stress in db/db mice islets were consistent with the results of the gene expression analysis.
Conclusions/interpretation
Liraglutide increases beta cell mass not only by directly regulating cell kinetics, but also by suppressing oxidative and ER stress, secondary to amelioration of glucolipotoxicity.
Springer