| First Author | Han D | Year | 2013 |
| Journal | Genes Cells | Volume | 18 |
| Issue | 4 | Pages | 302-14 |
| PubMed ID | 23410183 | Mgi Jnum | J:214912 |
| Mgi Id | MGI:5604200 | Doi | 10.1111/gtc.12036 |
| Citation | Han D, et al. (2013) Induction of receptor for advanced glycation end products by insufficient leptin action triggers pancreatic beta-cell failure in type 2 diabetes. Genes Cells 18(4):302-14 |
| abstractText | Glucolipotoxicity, which is exerted by free fatty acids (FFA) and prolonged hyperglycemia, is implicated in pancreatic beta-cell failure in diabetes. Pattern recognition receptors such as receptor for advanced glycation end products (RAGE) and toll-like receptors 2 and 4 could mediate danger signals in beta-cells. We examined whether RAGE contributes to beta-cell failure in a type 2 diabetes mouse model. Pancreatic islets were isolated from ob/ob, db/db, diet-induced obesity (DIO), RAGE-null (RAGE(-/-) ), and RAGE(+/+) wild-type (WT) control mice and dispersed into single cells for flow cytometry. RAGE expression was detected in insulin-positive beta-cells of ob/ob and db/db mice, but not of WT, DIO, or RAGE(-/-) mice: thus, inadequate leptin receptor signaling and RAGE expression may be linked. Compared with RAGE(+/+) db/db mice, RAGE(-/-) db/db mice showed higher beta-cell number and mass with less apoptosis as well as glucose tolerance with higher insulin secretion without any differences in serum levels of FFA and adiponectin. Palmitate or oleate pretreatment combined with a leptin antagonist induced RAGE expression, AGE-elicited apoptosis, and impaired glucose-stimulated insulin secretion by advanced glycation end products (AGE) in MIN6 cells. FFA elevation with concomitant AGE formation during prolonged hyperglycemia could cause beta-cell damage through insufficient leptin action and subsequent RAGE induction in type 2 diabetes. |
