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.
AIMS/HYPOTHESIS: We investigated the molecular mechanism by which the humanglucagon-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.
Authors: Jan Nygaard Jensen; Erin Cameron; Maria Veronica R Garay; Thomas W Starkey; Roberto Gianani; Jan Jensen Journal: Gastroenterology Date: 2005-03 Impact factor: 22.682
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Authors: Thomas A Buchanan; Anny H Xiang; Ruth K Peters; Siri L Kjos; Aura Marroquin; Jose Goico; Cesar Ochoa; Sylvia Tan; Kathleen Berkowitz; Howard N Hodis; Stanley P Azen Journal: Diabetes Date: 2002-09 Impact factor: 9.461
Authors: Stanley S Schwartz; Solomon Epstein; Barbara E Corkey; Struan F A Grant; James R Gavin; Richard B Aguilar Journal: Diabetes Care Date: 2016-02 Impact factor: 19.112