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• W2078923086 abstract "Objective: Progressive β-cell dysfunction and loss of β-cell mass are fundamental pathogenic features of type 2 diabetes. To examine if anti-diabetic reagents, such as insulin, pioglitazone (pio), and alogliptin (alo), have protective effects on β-cell mass and function in vivo, we treated obese diabetic db/db mice with these reagents. Methods: Male db/db mice were treated with a chow including pio, alo, or both of them from 8 to 16 weeks of age. Insulin glargine (gla) was daily injected subcutaneously during the same period. Results: At 16 weeks of age, untreated db/db mice revealed marked increase of HbA1c level, whereas those treated with pio, pio + alo, or insulin revealed the almost same HbA1c levels as non-diabetic db/m mice. Islet mass evaluated by direct counting in the whole pancreas and insulin content in isolated islets were preserved in pio, pio + alo and gla groups compared with untreated or alo groups, and there was no difference among pio, pio + alo and gla groups. To precisely evaluate islet β-cell functions, islet perifusion analysis was performed. In pio, pio + alo and gla groups, biphasic insulin secretion was preserved compared with untreated or alo groups. In particular, pio + alo as well as gla therapy preserved almost normal insulin secretion, although pio therapy improved partially. To examine the mechanism how these reagents exerted beneficial effects on β-cells, we evaluated expression levels of various factors which are potentially important for β-cell functions by real-time RT-PCR and immunohistochemistry. The results showed that expression levels of MafA and GLP-1 receptor were markedly decreased in untreated and alo groups, but not in pio, pio + alo and gla groups. Conclusion: Combination therapy with pio and alo almost completely normalized β-cell functions in vivo, which was comparable with gla treatment." @default.
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• W2078923086 date "2011-01-01" @default.
• W2078923086 modified "2023-09-25" @default.
• W2078923086 title "Effect of alogliptin, pioglitazone and glargine on pancreatic β-cells in diabetic db/db mice" @default.
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• W2078923086 doi "https://doi.org/10.1016/j.bbrc.2010.12.021" @default.
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