| First Author | Baggio LL | Year | 2006 |
| Journal | Diabetes | Volume | 55 |
| Issue | 6 | Pages | 1562-70 |
| PubMed ID | 16731818 | Mgi Jnum | J:111885 |
| Mgi Id | MGI:3655000 | Doi | 10.2337/db05-1502 |
| Citation | Baggio LL, et al. (2006) Lymphocytic Infiltration and Immune Activation in Metallothionein Promoter-Exendin-4 (MT-Exendin) Transgenic Mice. Diabetes 55(6):1562-70 |
| abstractText | Glucagon-like peptide 1 (GLP-1) exhibits considerable potential for the treatment of type 2 diabetes because of its effects on stimulation of insulin secretion and the inhibition of gastric emptying, appetite, and glucagon secretion. However, native GLP-1 undergoes rapid enzymatic inactivation, prompting development of long-acting degradation-resistant GLP-1 receptor agonists such as exendin-4 (Ex-4). To study the consequences of sustained exposure to Ex-4, we generated metallothionein promoter-exendin-4 (MT-Exendin) mice that continuously express a proexendin-4 transgene in multiple murine tissues. We now report that MT-Exendin mice develop extensive tissue lymphocytic infiltration with increased numbers of CD4(+) and CD8a(+) cells in the liver and/or kidney and increased numbers of B220(+) cells present in the pancreas and liver. MT-Exendin mice generate antibodies directed against Ex-4, exendin NH(2)-terminal peptide (ENTP), and proexendin-4 as well as antibodies that cross-react with native GLP-1. Furthermore, lymphocytes isolated from MT-Exendin mice proliferate in response to proexendin-4 but not after exposure to Ex-4 or ENTP. These findings demonstrate that expression of a proexendin-4 transgene may be associated with activation of humoral and cellular immune responses in mice. |
