| First Author | Shirakawa J | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 29 | Pages | 25467-76 |
| PubMed ID | 21613229 | Mgi Jnum | J:175391 |
| Mgi Id | MGI:5285475 | Doi | 10.1074/jbc.M110.217216 |
| Citation | Shirakawa J, et al. (2011) Protective effects of dipeptidyl peptidase-4 (DPP-4) inhibitor against increased beta cell apoptosis induced by dietary sucrose and linoleic acid in mice with diabetes. J Biol Chem 286(29):25467-76 |
| abstractText | Chronic exposure to high glucose and fatty acid levels caused by dietary sugar and fat intake induces beta cell apoptosis, leading to the exacerbation of type 2 diabetes. Oleic acid and linoleic acid are two major dietary fatty acids, but their effects in diabetes are unclear. We challenged beta cell-specific glucokinase haploinsufficient (Gck(+/-)) mice with a diet containing sucrose and oleic acid (SO) or sucrose and linoleic acid (SL) and analyzed beta cell apoptosis. In Gck(+/-) but not wild-type mice, SL significantly decreased the beta cell mass and beta cell proportion in islet cells arising from increased apoptosis to a greater degree than did SO. The mRNA expression of SREBP-1c was significantly higher, and that of E-cadherin was significantly lower in the islets of Gck(+/-) mice fed SL compared with mice fed SO. We next evaluated monotherapy with desfluorositagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in these mouse groups. DPP-4 inhibitor protected against beta cell apoptosis, restored the beta cell mass, and normalized islet morphology in Gck(+/-) mice fed SL. DPP-4 inhibition normalized the changes in the islet expression of SREBP-1c and E-cadherin mRNA induced by the SL diet. Furthermore, linoleic acid induced beta cell apoptosis to a greater degree in the presence of high glucose levels than in the presence of low glucose levels in vitro in islets and MIN6 cells, whereas a GLP-1 receptor agonist prevented apoptosis. In conclusion, SL exacerbated beta cell apoptosis in diabetic Gck(+/-) mice but not in euglycemic wild-type mice, and DPP-4 inhibition protected against these effects. |
