| First Author | Hoang M | Year | 2019 |
| Journal | Endocrinology | Volume | 160 |
| Issue | 12 | Pages | 2825-2836 |
| PubMed ID | 31580427 | Mgi Jnum | J:281725 |
| Mgi Id | MGI:6379512 | Doi | 10.1210/en.2018-00936 |
| Citation | Hoang M, et al. (2019) The Loss of ARNT/HIF1beta in Male Pancreatic beta-Cells Is Protective Against High-Fat Diet-Induced Diabetes. Endocrinology 160(12):2825-2836 |
| abstractText | The transcription factor aryl hydrocarbon receptor nuclear translocator (ARNT)/hypoxia-inducible factor (HIF)-1beta (ARNT/HIF1beta) plays a key role in maintaining beta-cell function and has been shown to be one of the most downregulated transcription factors in islets from patients with type 2 diabetes. We have shown a role for ARNT/HIF1beta in glucose sensing and insulin secretion in vitro and no defects in in vivo glucose homeostasis. To gain a better understanding of the role of ARNT/HIF1beta in the development of diabetes, we placed control (+/+/Cre) and beta-cell-specific ARNT/HIF1beta knockout (fl/fl/Cre) mice on a high-fat diet (HFD). Unlike the control (+/+/Cre) mice, HFD-fed fl/fl/Cre mice had no impairment in in vivo glucose tolerance. The lack of impairment in HFD-fed fl/fl/Cre mice was partly due to an improved islet glucose-stimulated NADPH/NADP+ ratio and glucose-stimulated insulin secretion. The effects of the HFD-rescued insulin secretion in fl/fl/Cre islets could be reproduced by treating low-fat diet (LFD)-fed fl/fl/Cre islets with the lipid signaling molecule 1-monoacylglcyerol. This suggests that the defects seen in LFD-fed fl/fl/Cre islet insulin secretion involve lipid signaling molecules. Overall, mice lacking ARNT/HIF1beta in beta-cells have altered lipid signaling in vivo and are resistant to an HFD's ability to induce diabetes. |
