Post-transcriptional control by RNA-binding proteins in diabetes and its related complications

Zhang, Shiyu; Yang, Xiao-Hua; Jiang, Miao; Ma, Lianhua; Hu, Ji; Zhang, Honghong

doi:10.3389/fphys.2022.953880

Cited by 4 publications

(2 citation statements)

References 139 publications

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“…Other proteins in the same family, like RBPs, are involved in various processes in pancreatic β-cells, including insulin synthesis and secretion. Their expression in glucose-induced β-cells is mediated by the insulin receptor signaling pathway, which can decrease their expression [73].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Probiotic Supplements on Metabolic Parameters of People with Type 2 Diabetes in Greece—A Randomized, Double-Blind, Placebo-Controlled Study

Zikou,

Dovrolis,

Dimosthenopoulos

et al. 2023

Nutrients

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The role of probiotic supplementation in type 2 diabetes (T2D) treatment is controversial. The present study aimed to assess the effects of a multi-strain probiotic supplement (LactoLevureR (containing Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii)) over 6 months, primarily on glycemic control as well as on lipid levels and alterations in the gut microbiome, among individuals with T2D residing in Greece. A total of 91 adults with T2D (mean age [±SD] 65.12 ± 10.92 years, 62.6% males) were randomized to receive the probiotic supplement or a matching placebo capsule, once daily, for 6 months. Blood chemistries and anthropometric parameters were conducted every 3 months, and stool samples were collected at baseline and at 6 months. Significant reductions in HbA1c, fasting blood glucose, and total cholesterol were observed in participants treated with the probiotic supplement (n = 46) compared to the controls (n = 45), even after adjustment for a greater decrease in adiposity (waist circumference). Although there were no statistically significant differences in the diversity of the gut microbiome (α and β diversity), the administration of probiotics did influence several genera, metabolites, and key enzymes associated with diabetes. Overall, the administration of the multi-strain probiotic LactoLevureR over a 6-month period in individuals with T2D was well-tolerated and had a positive impact on metabolic parameters, alongside improvements in indices of adiposity.

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Section: Discussionmentioning

confidence: 99%

The Effect of Probiotic Supplements on Metabolic Parameters of People with Type 2 Diabetes in Greece—A Randomized, Double-Blind, Placebo-Controlled Study

Zikou,

Dovrolis,

Dimosthenopoulos

et al. 2023

Nutrients

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“…Splicing factors are essential in regulating RNA splicing by recognizing specific cis-regulatory sequences 20 . The expression levels of some spliceosome and RNA binding proteins (RBPs), which were significantly altered in insulin-resistant or T2D donors, were associated with the progress of the disease 21 , 22 . Splicing factors, NOVA1 , NOVA2 , ELAVL4 , PRFP8 / PRP8 , etc., which encode splicing factors or major spliceosomes, regulate insulin secretion or β-cell survivals 10 , 23 .…”

Section: Introductionmentioning

confidence: 99%

Regulation of endocrine cell alternative splicing revealed by single-cell RNA sequencing in type 2 diabetes pathogenesis

Wang,

Wen,

Chen

et al. 2024

Commun Biol

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The prevalent RNA alternative splicing (AS) contributes to molecular diversity, which has been demonstrated in cellular function regulation and disease pathogenesis. However, the contribution of AS in pancreatic islets during diabetes progression remains unclear. Here, we reanalyze the full-length single-cell RNA sequencing data from the deposited database to investigate AS regulation across human pancreatic endocrine cell types in non-diabetic (ND) and type 2 diabetic (T2D) individuals. Our analysis demonstrates the significant association between transcriptomic AS profiles and cell-type-specificity, which could be applied to distinguish the clustering of major endocrine cell types. Moreover, AS profiles are enabled to clearly define the mature subset of β-cells in healthy controls, which is completely lost in T2D. Further analysis reveals that RNA-binding proteins (RBPs), heterogeneous nuclear ribonucleoproteins (hnRNPs) and FXR1 family proteins are predicted to induce the functional impairment of β-cells through regulating AS profiles. Finally, trajectory analysis of endocrine cells suggests the β-cell identity shift through dedifferentiation and transdifferentiation of β-cells during the progression of T2D. Together, our study provides a mechanism for regulating β-cell functions and suggests the significant contribution of AS program during diabetes pathogenesis.

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Mbnl1-mediated alternative splicing of circMlxipl regulates Rbbp6-involved ChREBP turnover to inhibit lipotoxicity-induced β-cell damage

Gong,

Wei,

Cao

et al. 2024

Mol Med

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Background Diabetes, a global epidemic, is the leading cause of mortality globally. The aim of this study is to get better understanding of pathophysiology of diabetes. Methods Palmitic acid (PA)-treated β-cells, db/db mice and high fat diet (HFD)-fed mouse model of type 2 diabetes were established. H&E was used to assess the histological changes of pancreas. IHC, FISH, western blot or qRT-PCR was employed to detect the expression of key molecules in primary islets or lipotoxic β-cells. Cell behaviors were detected by MTT, EdU incorporation assay, TUNEL assay and glucose-induced insulin secretion (GSIS). The associations among circMlxipl, Mbnl1 and Rbbp6 were validated by RIP and RNA pull-down assays, and the direct binding between Hdac3 and Mbnl1 promoter was examined by ChIP and luciferase assays. Co-IP was employed to assess the interaction between ChREBP and Rbbp6, as well as the ubiquitination of ChREBP. Results Hdac3 and ChREBP were upregulated, but Mbnl1 and circMlxipl were downregulated in islets from diabetic mice and lipotoxic β-cells. Mbnl1 overexpression protected against PA-induced impairments in lipotoxic β-cells through modulating back-splicing of circMlxipl and suppressing ChREBP. Hdac3 served as a transcriptional repressor of Mbnl1, and it was implicated in circMlxipl-mediated protection via regulating ChREBP expression in lipotoxic β-cells. Lack of circMlxipl inhibited Rbbp6-mediated ubiquitin-proteasomal degradation of ChREBP in lipotoxic β-cells. In vivo studies revealed that Hdac3 knockdown or Mbnl1 overexpression alleviated diabetes symptoms through circMlxipl-regulated ChREBP in diabetic mice. Conclusion Mbnl1-mediated alternative splicing of circMlxipl regulates Rbbp6-involved ChREBP turnover to inhibit lipotoxicity-induced β-cell damage.

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Post-transcriptional control by RNA-binding proteins in diabetes and its related complications

Cited by 4 publications

References 139 publications

The Effect of Probiotic Supplements on Metabolic Parameters of People with Type 2 Diabetes in Greece—A Randomized, Double-Blind, Placebo-Controlled Study

The Effect of Probiotic Supplements on Metabolic Parameters of People with Type 2 Diabetes in Greece—A Randomized, Double-Blind, Placebo-Controlled Study

Regulation of endocrine cell alternative splicing revealed by single-cell RNA sequencing in type 2 diabetes pathogenesis

Mbnl1-mediated alternative splicing of circMlxipl regulates Rbbp6-involved ChREBP turnover to inhibit lipotoxicity-induced β-cell damage

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