| First Author | Liu W | Year | 2018 |
| Journal | Endocrinology | Volume | 159 |
| Issue | 9 | Pages | 3235-3244 |
| PubMed ID | 30052841 | Mgi Jnum | J:277626 |
| Mgi Id | MGI:6342309 | Doi | 10.1210/en.2018-00451 |
| Citation | Liu W, et al. (2018) Olfactomedin 4 Deletion Improves Male Mouse Glucose Intolerance and Insulin Resistance Induced by a High-Fat Diet. Endocrinology 159(9):3235-3244 |
| abstractText | Glucose-stimulated insulin secretion (GSIS) is essential for blood glucose homeostasis and is impaired in type 2 diabetes mellitus. Understanding the regulatory components of GSIS has clinical implications for diabetes treatment. In this study, we found that olfactomedin 4 (OLFM4) is endogenously expressed in pancreatic islet beta cells and further investigated its potential roles in glucose homeostasis and the pathogenesis of type 2 diabetes using mouse models. Olfm4-deficient mice showed significantly improved glucose tolerance and significantly increased insulin levels after glucose challenge compared with wild-type (WT) mice. GSIS, mitochondrial ATP production, and mitochondrial respiration were all significantly increased in islets isolated from Olfm4-deficient mice compared with those isolated from WT mice. In a high-fat diet (HFD)-induced diabetic mouse model, the increase in insulin levels after glucose challenge was significantly higher in Olfm4-deficient mice compared with WT mice. The impaired glucose tolerance and insulin resistance in HFD-fed mice were improved by loss of Olfm4. Olfm4 was found to be mainly localized in the mitochondria and interacts with GRIM-19 (a gene associated with retinoid-interferon mortality) in Min6 pancreatic beta cells. Collectively, these studies suggest that Olfm4 negatively regulates GSIS. OLFM4 may represent a potential therapeutic target for impaired glucose tolerance and patients with type 2 diabetes. |
