| First Author | Werneck-de-Castro JP | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 2079 |
| PubMed ID | 33483593 | Mgi Jnum | J:300456 |
| Mgi Id | MGI:6502183 | Doi | 10.1038/s41598-021-81457-4 |
| Citation | Werneck-de-Castro JP, et al. (2021) The RNA-binding protein LARP1 is dispensable for pancreatic beta-cell function and mass. Sci Rep 11(1):2079 |
| abstractText | Mechanistic target of rapamycin complex 1 (mTORC1) deficiency or chronic hyperactivation in pancreatic beta-cells leads to diabetes. mTORC1 complexes with La-related protein 1 (LARP1) to specifically regulate the expression of 5' terminal oligopyrimidine tract (5'TOP) mRNAs which encode proteins of the translation machinery and ribosome biogenesis. Here we show that LARP1 is the most expressed LARP in mouse islets and human beta-cells, being 2-4-fold more abundant than LARP1B, a member of the family that also interacts with mTORC1. Interestingly, beta-cells from diabetic patients have higher LARP1 and LARP1B expression. However, specific deletion of Larp1 gene in beta-cells (beta-Larp1KO mice) did not impair insulin secretion and glucose metabolism in male and female mice. High fat or high branched-chain amino acid (BCAA) diets did not disturb glucose homeostasis compared to control littermates up to 8 weeks; BCAA diet slightly impaired glucose tolerance in the beta-Larp1KO mice at 16 weeks. However, no differences in plasma insulin levels, non-fasting glycemia and beta-cell mass were observed in the beta-Larp1KO mice. In conclusion, LARP1 is the most abundant LARP in mouse islets and human beta-cells, and it is upregulated in diabetic subjects. However, genetically disruption of Larp1 gene did not impact glucose homeostasis in basal and diabetogenic conditions, suggesting no major role for LARP1 in beta-cells. |
