| First Author | Francisco AB | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 25 | Pages | 22275-82 |
| PubMed ID | 21536682 | Mgi Jnum | J:174809 |
| Mgi Id | MGI:5141194 | Doi | 10.1074/jbc.M111.239418 |
| Citation | Francisco AB, et al. (2011) Haploid insufficiency of suppressor enhancer Lin12 1-like (SEL1L) protein predisposes mice to high fat diet-induced hyperglycemia. J Biol Chem 286(25):22275-82 |
| abstractText | Increasing evidence suggests that endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of type 2 diabetes mellitus. SEL1L is an ER membrane protein that is highly expressed in the pancreatic islet and acinar cells. We have recently reported that a deficiency of SEL1L causes systemic ER stress and leads to embryonic lethality in mice. Here we show that mice with one functional allele of Sel1l (Sel1l(+/-)) are more susceptible to high fat diet (HFD)-induced hyperglycemia. Sel1l(+/-) mice have a markedly reduced beta-cell mass as a result of decreased beta-cell proliferation. Consequently, Sel1l(+/-) mice are severely glucose-intolerant and exhibit significantly retarded glucose-stimulated insulin secretion. Pancreatic islets from Sel1l(+/-) mice stimulated with a high concentration of glucose in vitro express significantly higher levels of unfolded protein response genes than those from wild-type control mice. Furthermore, dominant-negative interference of SEL1L function in insulinoma cell lines severely impairs, whereas overexpression of SEL1L efficiently improves protein secretion. Taken together, our results indicate that haploid insufficiency of SEL1L predispose mice to high fat diet-induced hyperglycemia. Our findings highlight a critical and previously unknown function for SEL1L in regulating adult beta-cell function and growth. |
