The aim was to compare the protective effects of pioglitazone (PIO) and/or liraglutide (LIRA) on β-cells with the progression of diabetes. Male db/db mice were treated with PIO and/or LIRA for 2 weeks in an early and advanced stage. In an early stage insulin biosynthesis and secretion were markedly increased by PIO and LIRA which was not observed in an advanced stage. In concomitant with such phenomena, expression levels of various β-cell-related factors were up-regulated by PIO and LIRA only in an early stage. Furthermore, β-cell mass was also increased by the treatment only in an early stage. Although there was no difference in apoptosis ratio between the two stages, β-cell proliferation was augmented by the treatment only in an early stage. In conclusion, protective effects of pioglitazone and/or liraglutide on β-cells were more powerful in an early stage of diabetes compared to an advanced stage.
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