Differential Impact of Glucose Administered Intravenously and Orally on Circulating miR-375 Levels in Human Subjects

Yan, Xin; Wang, Zhen; Westberg-Rasmussen, Sidse; Tarbier, Marcel; Rathjen, Thomas; Tattikota, Sudhir Gopal; Peck, Bailey C. E.; Kanke, Matt; Oxvig, Claus; Frystyk, Jan; Starup-Linde, Jakob; Sethupathy, Praveen; Friedländer, Marc R.; Gregersen, Søren; Poy, Matthew N.

doi:10.1210/jc.2017-01365

Cited by 7 publications

(3 citation statements)

References 31 publications

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“…The GLP2 following nutrient uptake increases the level of miR-375 and improves lipid and glucose metabolism. In contrast, knock out mir-375 results in reduced βcell mass and hyperglycemia[33].…”

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confidence: 94%

Incretins and microRNAs: Interactions and physiological relevance

Radbakhsh

Sathyapalan

Banach

et al. 2020

Pharmacological Research

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MicroRNAs (miRNA) are one class of the small regulatory RNAs that can impact the expression of numerous genes including incretin hormones and their G protein-coupled receptors. Incretin peptides, including GLP-1, GLP-2, and GIP, are released from the gastrointestinal tract and have an crucial role in the glucose hemostasis and pancreatic beta-cell function. These hormones and their analogs with a longer half-life, glucagon like peptide-1 receptor agonists (GLP1RA), modify the expression of miRNAs. Dipeptidyl peptidase IV (DPP-4) is an enzyme that degrades the incretin hormones and is inactivated by DPP-4 inhibitors, which are a class of compounds used in the management of type 2 diabetes. DPP-4 inhibitors may also increase or reduce the expression of miRNAs. In this review, we describe the possible interactions between miRNAs and incretin hormones and the relevance of such interactions to physiological processes and diseases.

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confidence: 94%

Incretins and microRNAs: Interactions and physiological relevance

Radbakhsh

Sathyapalan

Banach

et al. 2020

Pharmacological Research

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“…Both up and down regulation result in a reduction of blood glucose by improving beta-cell function and increasing insulin secretion. Little is known about regulation of miRNA expression by GIP, though there is a report on overexpression of miR-375 stimulated also by GIP [96]. The authors suggest that this circulating miRNA may originate from enteroendocrine cells or the brain, and could exert a diverse effect on lipid and glucose metabolism in the liver.…”

Section: Discussionmentioning

confidence: 99%

Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis

et al. 2020

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Nutrient excess enhances glucose-dependent insulinotropic polypeptide (GIP) secretion, which may in turn contribute to the development of liver steatosis. We hypothesized that elevated GIP levels in obesity may affect markers of liver injury through microRNAs. The study involved 128 subjects (body mass index (BMI) 25–40). Fasting and postprandial GIP, glucose, insulin, and lipids, as well as fasting alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), cytokeratin-18, fibroblast growth factor (FGF)-19, and FGF-21 were determined. TaqMan low density array was used for quantitative analysis of blood microRNAs. Fasting GIP was associated with ALT [β = 0.16 (confidence interval (CI): 0.01–0.32)], triglycerides [β = 0.21 (95% CI: 0.06–0.36], and FGF-21 [β = 0.20 (95%CI: 0.03–0.37)]; and postprandial GIP with GGT [β = 0.17 (95%CI: 0.03–0.32)]. The odds ratio for elevated fatty liver index (>73%) was 2.42 (95%CI: 1.02–5.72) for high GIP versus low GIP patients. The miRNAs profile related to a high GIP plasma level included upregulated miR-136-5p, miR-320a, miR-483-5p, miR-520d-5p, miR-520b, miR-30e-3p, and miR-571. Analysis of the interactions of these microRNAs with gene expression pathways suggests their potential contribution to the regulation of the activity of genes associated with insulin resistance, fatty acids metabolism, and adipocytokines signaling. Exaggerated fasting and postprandial secretion of GIP in obesity are associated with elevated liver damage markers as well as FGF-21 plasma levels. Differentially expressed microRNAs suggest additional, epigenetic factors contributing to the gut–liver cross-talk.

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“…For example, abnormal expression of several miRNAs has been observed in response to a glucose challenge in healthy subjects [11], or in different tissues of T2D subjects [12]. Intriguingly, upregulation of serum miR-31 has been reported in a group of T2D patients with microvascular complications (retinopathy, neuropathy or nephropathy), although the study in question did not reveal the miR-31 expression level in each of the complications under scrutiny [13].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR-31 in Diabetic Nephropathy and its Relationship with Inflammation

Rovira‐Llopis

Escribano-López

Díaz-Morales

et al. 2018

Cell Physiol Biochem

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Background/Aims: There is a lack of reliable biological markers for the early diagnosis of diabetic nephropathy (DN) during type 2 diabetes. In this pilot study we aim to assess whether miR-31 levels are modulated by the presence of DN and whether the expression of this miRNA is related to leukocyte-endothelial interactions and inflammation. Methods: Thirty-one T2D patients were enrolled in this pilot study; 18 with no diabetic complications and 13 with diabetic nephropathy. 24 non-diabetic subjects and 13 T2D patients with retinopathy (absent of other complications) were included to test the specificity of miR-31. Following anthropometric and biochemical evaluation, serum miR-31 levels were assessed by Real Time-PCR. Leukocyte-endothelial interactions were evaluated by a parallel flow chamber in vitro model. Serum TNFα, IL-6 and ICAM-1 levels were determined by XMAP-technology in a flow cytometry-based Luminex 200 instrument. Results: Serum miR-31 levels were similar between control and T2D subjects. However, T2D patients with DN displayed reduced levels of miR-31 with respect to patients without complications. This decrease in miR-31 was more pronounced in patients with macroalbuminuria than in those with microalbuminuria and was specific for DN, since patients with retinopathy displayed unaltered miR-31 levels. The presence of DN involved a lower leukocyte rolling velocity and an increased rolling flux and adhesion. miR-31 levels were positively correlated with leukocyte rolling velocity and negatively associated to leukocyte adhesion, TNFα, IL-6 and ICAM-1 levels. Conclusion: Serum miR-31 may be a biomarker for DN in T2D patients. The regulation of this miRNA seems to be related to the recruitment of leukocytes to vascular walls induced by pro-inflammatory and adhesion molecules.

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Differential Impact of Glucose Administered Intravenously and Orally on Circulating miR-375 Levels in Human Subjects

Abstract: The present findings show levels of miR-375 increase following administration of an OGTT and, in light of its enrichment in cells of the gut, suggest that the gastrointestinal tract may play an important role in the abundance and function of this miRNA in the blood.

Cited by 7 publications

References 31 publications

Incretins and microRNAs: Interactions and physiological relevance

Incretins and microRNAs: Interactions and physiological relevance

Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis

Downregulation of miR-31 in Diabetic Nephropathy and its Relationship with Inflammation

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