| First Author | Guo X | Year | 2020 |
| Journal | Metabolism | Volume | 109 |
| Pages | 154290 | PubMed ID | 32522488 |
| Mgi Jnum | J:298055 | Mgi Id | MGI:6457189 |
| Doi | 10.1016/j.metabol.2020.154290 | Citation | Guo X, et al. (2020) Mof regulates glucose level via altering different alpha-cell subset mass and intra-islet glucagon-like peptide-1, glucagon secretion. Metabolism 109:154290 |
| abstractText | BACKGROUND: Males absent on the first (Mof) is implicated in gene control of diverse biological processes, such as cell growth, differentiation, apoptosis and autophagy. However, the relationship between glucose regulation and Mof-mediated transcription events remains unexplored. We aimed to unravel the role of Mof in glucose regulation by using global and pancreatic alpha-cell-specific Mof-deficient mice in vivo and alpha-TC1-6 cell line in vitro. METHODS: We used tamoxifen-induced temporal Mof-deficient mice first to show Mof regulate glucose homeostasis, islet cell proportions and hormone secretion. Then we used alpha-cell-specific Mof-deficient mice to clarify how alpha-cell subsets and beta-cell mass were regulated and corresponding hormone level alterations. Ultimately, we used small interfering RNA (siRNA) to knockdown Mof in alpha-TC1-6 and unravel the mechanism regulating alpha-cell mass and glucagon secretion. RESULTS: Mof was mainly expressed in alpha-cells. Global Mof deficiency led to lower glucose levels, attributed by decreased alpha/beta-cell ratio and glucagon secretion. alpha-cell-specific Mof-deficient mice exhibited similar alterations, with more reduced prohormone convertase 2 (PC2)-positive alpha-cell mass, responsible for less glucagon, and enhanced prohormone convertase 1 (PC1/3)-positive alpha-cell mass, leading to more glucagon-like peptide-1 (GLP-1) secretion, thus increased beta-cell mass and insulin secretion. In vitro, increased DNA damage, dysregulated autophagy, enhanced apoptosis and altered cell fate factors expressions upon Mof knockdown were observed. Genes and pathways linked to impaired glucagon secretion were uncovered through transcriptome sequencing. CONCLUSION: Mof is a potential interventional target for glucose regulation, from the aspects of both alpha-cell subset mass and glucagon, intra-islet GLP-1 secretion. Upon Mof deficiency, Up-regulated PC1/3 but down-regulated PC2-positive alpha-cell mass, leads to more GLP-1 and insulin but less glucagon secretion, and contributed to lower glucose level. |
