دورية أكاديمية
The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass.
| العنوان: | The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass. |
|---|---|
| المؤلفون: | Werneck-de-Castro JP; Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.; Miami VA Health Care System, Miami, FL, 33136, USA., Peçanha FLM; Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA., Silvestre DH; Institute of Nutrition Josué de Castro, Federal University of Rio de Janeiro, Rio de Janeiro, 21941090, Brazil., Bernal-Mizrachi E; Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. ebernalm@med.miami.edud.; Miami VA Health Care System, Miami, FL, 33136, USA. ebernalm@med.miami.edud. |
| المصدر: | Scientific reports [Sci Rep] 2021 Jan 22; Vol. 11 (1), pp. 2079. Date of Electronic Publication: 2021 Jan 22. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
| مواضيع طبية MeSH: | Autoantigens/*physiology , Insulin-Secreting Cells/*physiology , RNA-Binding Proteins/*physiology , Ribonucleoproteins/*physiology, Animals ; Autoantigens/genetics ; Autoantigens/metabolism ; Blood Glucose/metabolism ; Diet, High-Fat ; Female ; Homeostasis ; Humans ; Insulin-Secreting Cells/cytology ; Male ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Mice, Knockout ; Protein Binding ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Ribonucleoproteins/genetics ; Ribonucleoproteins/metabolism ; Up-Regulation ; SS-B Antigen |
| مستخلص: | Mechanistic target of rapamycin complex 1 (mTORC1) deficiency or chronic hyperactivation in pancreatic β-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 β-cells, being 2-4-fold more abundant than LARP1B, a member of the family that also interacts with mTORC1. Interestingly, β-cells from diabetic patients have higher LARP1 and LARP1B expression. However, specific deletion of Larp1 gene in β-cells (β-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 β-Larp1KO mice at 16 weeks. However, no differences in plasma insulin levels, non-fasting glycemia and β-cell mass were observed in the β-Larp1KO mice. In conclusion, LARP1 is the most abundant LARP in mouse islets and human β-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 β-cells. |
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| معلومات مُعتمدة: | I01 BX002728 United States BX BLRD VA; R01 DK073716 United States DK NIDDK NIH HHS; R01 DK084236 United States DK NIDDK NIH HHS; R01-DK073716 United States DK NIDDK NIH HHS |
| المشرفين على المادة: | 0 (Autoantigens) 0 (Blood Glucose) 0 (Larp1 protein, mouse) 0 (RNA-Binding Proteins) 0 (Ribonucleoproteins) EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) |
| تواريخ الأحداث: | Date Created: 20210123 Date Completed: 20211013 Latest Revision: 20231213 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7822907 |
| DOI: | 10.1038/s41598-021-81457-4 |
| PMID: | 33483593 |
| قاعدة البيانات: | MEDLINE |
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