| First Author | Kawashima S | Year | 2011 |
| Journal | Biochem Biophys Res Commun | Volume | 404 |
| Issue | 1 | Pages | 534-40 |
| PubMed ID | 21144823 | Mgi Jnum | J:167443 |
| Mgi Id | MGI:4868297 | Doi | 10.1016/j.bbrc.2010.12.021 |
| Citation | Kawashima S, et al. (2011) Effect of alogliptin, pioglitazone and glargine on pancreatic beta-cells in diabetic db/db mice. Biochem Biophys Res Commun 404(1):534-40 |
| abstractText | Objective: Progressive beta-cell dysfunction and loss of beta-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 beta-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 16weeks of age. Insulin glargine (gla) was daily injected subcutaneously during the same period. Results: At 16weeks 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 beta-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 beta-cells, we evaluated expression levels of various factors which are potentially important for beta-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 beta-cell functions in vivo, which was comparable with gla treatment. |
