Dataset Information

Elevation of Circulating miR-210 Participates in the Occurrence and Development of Type 2 Diabetes Mellitus and Its Complications

ABSTRACT:

Objective

Circulating miRNAs are acclaimed biomarkers to predict the occurrence and progression of type 2 diabetes mellitus (T2DM). This study is aimed at analyzing the correlation of circulating miR-210 level and obesity-associated T2DM and then investigating the underlying mechanism of circulating miR-210 in T2DM.

Methods

Totally, 137 serum samples from patients with T2DM were collected; meanwhile, the demographic, general, and clinical hematological characteristics, disease history, and dietary patterns were recorded. The miR-210 level in exosomes from serum was detected by qRT-PCR. Then, the correlations of BMI or miR-210 level with patients' clinical characteristics were analyzed. Furthermore, the miR-210 level was detected in T2DM related various cells under high glucose condition. Meanwhile, the expression of carbohydrate responsive element binding protein (ChREBP) and hypoxia-inducible factor 1α (HIF-1α) was measured by western blotting.

Results

The miR-210 level in exosomes from serum was obviously elevated in the BMI > 24 group compared with the BMI ≤ 24 group. Higher BMI was correlated with abnormal lipid metabolism and impaired liver function as well as higher miR-210 level. Notably, higher miR-210 level was also correlated with abnormal lipid metabolism, disease history, and dietary patterns. In addition, compared with normal cells, high glucose increased the miR-210 level in exosomes from cell culture supernatants as well as cells in HUVEC, VSMC, RAW 264.7, 3 T3-L1, SMC, and Beta-TC-6 cells, while it reduced the expression of ChREBP and HIF-1α.

Conclusions

Circulating miR-210 level was closely correlated with obesity-associated T2DM. Furthermore, higher miR-210 level might be implicated in the occurrence and development of T2DM and its complications.

SUBMITTER: Chen X

PROVIDER: S-EPMC9711992 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundIncreasing evidence indicates that immune response underlies the pathology of type 2 diabetes (T2D). Nevertheless, the specific inflammatory regulators involved in this pathogenesis remain unclear.MethodsWe systematically explored circulating inflammatory proteins that are causally associated with T2D via a bidirectional Mendelian randomization (MR) study and further investigated them in prevalent complications of T2D. Genetic instruments for 91 circulating inflammatory proteins were derived from a genome-wide association study (GWAS) that enrolled 14,824 predominantly European participants. Regarding the summary-level GWASs of type 2 diabetes, we adopted the largest meta-analysis of European population (74,124 cases vs. 824,006 controls) and a prospective nested case-cohort study in Europe (9,978 cases vs. 12,348 controls). Summary statistics for five complications of T2D were acquired from the FinnGen R9 repository. The inverse variance-weighted method was applied as the primary method for causal inference. MR-Egger, weighted median and maximum likelihood methods were employed as supplementary analyses. Results from the two T2D studies were combined in a meta-analysis. Sensitivity analyses and phenotype-wide association studies (PheWAS) were performed to detect heterogeneity and potential horizontal pleiotropy in the study.ResultsGenetic evidence indicated that elevated levels of TGF-α (OR = 1.16, 95% CI = 1.15-1.17) and CX3CL1 (OR = 1.30, 95% CI = 1.04-1.63) promoted the occurrence of T2D, and increased concentrations of FGF-21 (OR = 0.87, 95% CI = 0.81-0.93) and hGDNF (OR = 0.96, 95% CI = 0.95-0.98) mitigated the risk of developing T2D, while type 2 diabetes did not exert a significant influence on said proteins. Elevated levels of TGF-α were associated with an increased risk of ketoacidosis, neurological complications, and ocular complications in patients with T2D, and increased concentrations of FGF-21 were potentially correlated with a diminished risk of T2D with neurological complications. Higher levels of hGDNF were associated with an increased risk of T2D with peripheral vascular complications, while CX3CL1 did not demonstrate a significant association with T2D complications. Sensitivity analyses and PheWAS further ensure the robustness of our findings.ConclusionThis study determined four circulating inflammatory proteins that affected the occurrence of T2D, providing opportunities for the early prevention and innovative therapy of type 2 diabetes and its complications.