LncRNA-Malat1 is Involved in Lipotoxicity-Induced beta-cell Dysfunction and the Therapeutic Effect of Exendin-4 via Ptbp1
ENDOCRINOLOGY
Authors: Xiong, Li; Gong, Yingying; Wu, Liting; Li, Jin; He, Weiman; Zhu, Xiaonan; Xiao, Haipeng
Abstract
Increasing evidence indicates that long noncoding RNAs (lncRNAs) have crucial roles in various biological processes. However, the contribution of lncRNAs to beta-cell dysfunction and their roles in diabetes therapeutics remain poorly understood. The aim of this study was to identify the lncRNAs dysregulated in diabetic islets and to explore the lncRNAs involved in beta-cell function as potential therapeutic targets. By using RNA sequencing and real-time PCR, we identified thousands of lncRNAs in the islets of db/db mice and db/m littermate mice. Among the differentially expressed lncRNAs, lncRNA-Malat1 (metastasis-associated lung adenocarcinoma transcript 1) was reduced in the islets of db/db mice and palm itate-treated MIN6 cells. The results of TUNEL, Western blot and flow cytometric analyses, and GSIS assays revealed that Malat1 knockdown significantly induced beta-cell apoptosis and inhibited insulin secretion. Mechanistically, RNA immunoprecipitation showed that Malat1 enhanced polypyrimidine tract-binding protein 1 (Ptbp1) protein stability by direct interaction, thereby adjusting the ratio of pyruvate kinase muscle (PKM) isoforms 1 and 2 (PKM1/ PKM2). Moreover, luciferase assay and chromatin immunoprecipitation indicated that Malat1 was transcriptionally activated by pancreatic and duodenal homeobox 1 (Pdx1), through which exendin-4 alleviated lipotoxicity-induced beta-cell damage. In summary, our findings suggested the involvement of Malati in beta-cell dysfunction under diabetic conditions via the Malat1/Ptbp1/ PKM2 pathway. In addition, exendin-4 ameliorated beta-cell impairment by Pdx1-mediated Malat1 upregulation. Hence, Malat1 may serve as a therapeutic target for the treatment of type 2 diabetes.
Defect Analysis Of Quality Palm Kernel Meal Using Statistical Quality Control In Kernels Factory
INTERNATIONAL CONFERENCE ON MECHANICAL, ELECTRONICS, COMPUTER, AND INDUSTRIAL TECHNOLOGY
Authors: Sembiring, M. T.; Marbun, N. J.
Abstract
The production quality has an important impact retain the totality of characteristics of a product or service to pay attention to its capabilit ies to meet the needs that have been established. Quality criteria Palm Kernel Meal (PKM) set Factory kernel is as follows: oil content: max 8.50%, water content: max 12,00% and impurity content: max. 4.00% While the average quality of the oil content of 8.94%, the water content of 5.51%, and 8.45% impurity content. To identify the defective product quality PKM produced, then used a method of analysis using Statistical Quality Control (SQC). PKM Plant Quality Kernel shows the oil content was 0.44% excess of a predetermined maximum value, and 4.50% impurity content. With excessive PKM content of oil and dirt cause disability content of production for oil, amounted to 854.6078 kg PKM and 8643.193 kg impurity content of PKM. Analysis of the results of cause and effect diagram and SQC, the factors that lead to poor quality of PKM is Ampere second press oil expeller and hours second press oil expeller.