Role of microRNAs in the treatment of type 2 diabetes mellitus with Roux-en-Y gastric bypass

Zhu, Zheng; Yin, Jie; Li, D.C.; Mao, Zhongqi

doi:10.1590/1414-431x20175817

Cited by 15 publications

(16 citation statements)

References 24 publications

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“…From our small-RNAseq results, we identified miRNAs that showed significant concentration changes in patients when compared with non-DN controls (for patients with overt DN) or when compared with their previous non-MA urine collection cycle (for patients with IMA or PMA). Many of these miRNAs have been previously associated with kidney function, and have roles in the pathophysiology of diabetes 23 , 24 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , ...…”

Section: Discussionmentioning

confidence: 99%

“… AKR, Acute Kidney Rejection/Renal Graft Rejection; AKI, acute kidney injury; CKD, chronic kidney disease; DIKD, drug induced kidney damage, DN, diabetic nephropathy; Endo, endothelial dysfunction; EMT, epithelial–mesenchymal transition; EndMT, endothelial-mesenchymal transition; ESRD, end-stage renal disease; GD, gestational diabetes mellitus; IgA-N, IgA nephropathy; IGF, insulin-like growth factor; IGT, impaired glucose tolerance; LN-RD, lupus nephritis induced renal damage; MA, microalbuminuria; miRNA, microRNA; NS, nephrotic syndrome; PCKD, poly-cystic kidney disease; PKD, progressive kidney disease; PTEN, phosphatase and tensin homolog; RCC, renal cell carcinoma; Rfib, renal fibrosis: RIRI, renal ischemia-reperfusion injury; TGF, transforming growth factor; T1D, type 1 diabetes mellitus; T2D), type 2 diabetes mellitus. See references 23 , 24 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , …”

Section: Discussionmentioning

confidence: 99%

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Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes

Ghai

Bheda-Malge

et al. 2018

Kidney International Reports

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IntroductionDiabetic nephropathy (DN) is a form of progressive kidney disease that often leads to end-stage renal disease (ESRD). It is initiated by microvascular complications due to diabetes. Although microalbuminuria (MA) is the earliest clinical indication of DN among patients with type 1 diabetes (T1D), it lacks the sensitivity and specificity to detect the early onset of DN. Recently, microRNAs (miRNAs) have emerged as critical regulators in diabetes as well as various forms of kidney disease, including renal fibrosis, acute kidney injury, and progressive kidney disease. Additionally, circulating extracellular miRNAs, especially miRNAs packaged in extracellular vesicles (EVs), have garnered significant attention as potential noninvasive biomarkers for various diseases and health conditions.MethodsAs part of the University of Pittsburgh Epidemiology of Diabetes Complications (EDC) study, urine was collected from individuals with T1D with various grades of DN or MA (normal, overt, intermittent, and persistent) over a decade at prespecified intervals. We isolated EVs from urine and analyzed the small-RNA using NextGen sequencing.ResultsWe identified a set of miRNAs that are enriched in urinary EVs compared with EV-depleted samples, and identified a number of miRNAs showing concentration changes associated with DN occurrence, MA status, and other variables, such as hemoglobin A1c levels.ConclusionMany of the miRNAs associated with DN occurrence or MA status directly target pathways associated with renal fibrosis (including transforming growth factor-β and phosphatase and tensin homolog), which is one of the major contributors to the pathology of DN. These miRNAs are potential biomarkers for DN and MA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes

Ghai

Bheda-Malge

et al. 2018

Kidney International Reports

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“…PCOLCE2 , a collagen-related gene, is significantly reduced in T2DM ( 96 ). Zhu et al ( 97 ), identified that the expression level of hsa-miR-124-3p is decreased in patients with T2DM [9 high-body mass index (BMI) and 1 low-BMI] CTGF expression, a vital adjudicator of progressive pancreatic fibrosis, is elevated in T2DM ( 98 ). FAM105A is reported to be associated with T2DM ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of potential markers for type 2 diabetes mellitus via bioinformatics analysis

Lü

2020

Mol Med Rep

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Type 2 diabetes mellitus (T2dM) is a multifactorial and multigenetic disease, and its pathogenesis is complex and largely unknown. in the present study, microarray data (GSe201966) of β-cell enriched tissue obtained by laser capture microdissection were downloaded, including 10 control and 10 type 2 diabetic subjects. a comprehensive bioinformatics analysis of microarray data in the context of protein-protein interaction (PPi) networks was employed, combined with subcellular location information to mine the potential candidate genes for T2dM and provide further insight on the possible mechanisms involved. First, differential analysis screened 108 differentially expressed genes. Then, 83 candidate genes were identified in the layered network in the context of PPi via network analysis, which were either directly or indirectly linked to T2dM. of those genes obtained through literature retrieval analysis, 27 of 83 were involved with the development of T2dM; however, the rest of the 56 genes need to be verified by experiments. The functional analysis of candidate genes involved in a number of biological activities, demonstrated that 46 upregulated candidate genes were involved in 'inflammatory response' and 'lipid metabolic process', and 37 downregulated candidate genes were involved in 'positive regulation of cell death' and 'positive regulation of cell proliferation'. These candidate genes were also involved in different signaling pathways associated with 'Pi3K/akt signaling pathway', 'Rap1 signaling pathway', 'Ras signaling pathway' and 'MAPK signaling pathway', which are highly associated with the development of T2dM. Furthermore, a microrna (mir)-target gene regulatory network and a transcription factor-target gene regulatory network were constructed based on mirnet and networkanalyst databases, respectively. notably, hsa-mir-192-5p, hsa-mir-124-5p and hsa-mir-335-5p appeared to be involved in T2dM by potentially regulating the expression of various candidate genes, including procollagen c-endopeptidase enhancer 2, connective tissue growth factor and family with sequence similarity 105, member a, protein phosphatase 1 regulatory inhibitor subunit 1 a and cc motif chemokine receptor 4. Smad5 and Bcl6, as transcription factors, are regulated by ankyrin repeat domain 23 and transmembrane protein 37, respectively, which might also be used in the molecular diagnosis and targeted therapy of T2dM. Taken together, the results of the present study may offer insight for future genomic-based individualized treatment of T2dM and help determine the underlying molecular mechanisms that lead to T2dM.

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“…It is to be noted that most previous studies evaluating the circulating levels of miRNAs after gastric bypass were obtained in non-diabetic cohorts [96] , [97] , [98] , [99] . Furthermore, the small number of studies performed on Type 2 diabetes patients after bariatric surgery have compared circulating miRNA levels post-operatively only with the pre-surgery state (which is therefore an obese state) [100] , [101] , [102] . Thus, the differential levels of circulating miRNAs in these cohorts could be a consequence of weight loss rather than diabetes remission.…”

Section: Discussionmentioning

confidence: 99%

A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice

et al. 2020

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Background Bariatric surgery is an effective treatment for type 2 diabetes. Early post-surgical enhancement of insulin secretion is key for diabetes remission. The full complement of mechanisms responsible for improved pancreatic beta cell functionality after bariatric surgery is still unclear. Our aim was to identify pathways, evident in the islet transcriptome, that characterize the adaptive response to bariatric surgery independently of body weight changes. Methods We performed entero-gastro-anastomosis (EGA) with pyloric ligature in leptin-deficient ob/ob mice as a surrogate of Roux-en-Y gastric bypass (RYGB) in humans. Multiple approaches such as determination of glucose tolerance, GLP-1 and insulin secretion, whole body insulin sensitivity, ex vivo glucose-stimulated insulin secretion (GSIS) and functional multicellular Ca 2+ -imaging, profiling of mRNA and of miRNA expression were utilized to identify significant biological processes involved in pancreatic islet recovery. Findings EGA resolved diabetes, increased pancreatic insulin content and GSIS despite a persistent increase in fat mass, systemic and intra-islet inflammation, and lipotoxicity. Surgery differentially regulated 193 genes in the islet, most of which were involved in the regulation of glucose metabolism, insulin secretion, calcium signaling or beta cell viability, and these were normalized alongside changes in glucose metabolism, intracellular Ca 2+ dynamics and the threshold for GSIS. Furthermore, 27 islet miRNAs were differentially regulated, four of them hubs in a miRNA-gene interaction network and four others part of a blood signature of diabetes resolution in ob/ob mice and in humans. Interpretation Taken together, our data highlight novel miRNA-gene interactions in the pancreatic islet during the resolution of diabetes after bariatric surgery that form part of a blood signature of diabetes reversal. Funding European Union's Horizon 2020 research and innovation programme via the Innovative Medicines Initiative 2 Joint Undertaking (RHAPSODY), INSERM, Société Francophone du Diabète, Institut Benjamin Delessert, Wellcome Trust Investigator Award (212625/Z/18/Z), MRC Programme grants (MR/R022259/1, MR/J0003042/1, MR/L020149/1), Diabetes UK (BDA/11/0004210, BDA/15/0005275, BDA 16/0005485) project grants, National Science Foundation (310030–188447), Fondation de l'Avenir.

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Role of microRNAs in the treatment of type 2 diabetes mellitus with Roux-en-Y gastric bypass

Cited by 15 publications

References 24 publications

Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes

Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes

Identification of potential markers for type 2 diabetes mellitus via bioinformatics analysis

A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice

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