Kidney Res Clin Pract.  2021 Sep;40(3):383-391. 10.23876/j.krcp.21.015.

Urinary exosomal microRNA profiling in type 2 diabetes patients taking dipeptidyl peptidase-4 inhibitor compared with sulfonylurea

Affiliations
  • 1Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
  • 2Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
  • 3Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan, Republic of Korea

Abstract

Background
Dipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to have kidney-protective benefits. To elucidate how antidiabetic agents prevent diabetic kidney disease progression, it is important to investigate their effect on the kidney environment in type 2 diabetes mellitus (DM) patients. Herein, we investigated the expression pattern of urinary exosome-derived microRNA (miRNA) in patients taking a combination of DPP-4 inhibitor and metformin (DPP-4 inhibitor group) and compared them with patients taking a combination of sulfonylurea and metformin (sulfonylurea group).
Methods
This was a prospective study involving 57 patients with type 2 DM (DPP-4 inhibitor group, n = 34; sulfonylurea group, n = 23) and healthy volunteers (n = 7). We measured urinary exosomal miRNA using the NanoString nCounter miRNA array (NanoString Technologies) across the three groups (n = 4 per each group) and validated findings using real-time polymerase chain reaction.
Results
Twenty-one differentially expressed candidate miRNAs were identified, and six (let-7c-5p, miR-23a-3p, miR-26a-3p, miR-30d, miR-205, and miR-200a) were selected for validation. Validation showed no significant difference in miRNA expression between the DPP-4 inhibitor and sulfonylurea groups. Only miR-23a-3p was significantly overexpressed in the diabetes group compared with the control group (DPP-4 inhibitor vs. control, p = 0.01; sulfonylurea vs. control, p = 0.007). This trend was consistent even after adjusting for age, sex, and body mass index.
Conclusion
There was no significant difference in urine exosome miRNA expression between diabetic participants taking DPP-4 inhibitor and those taking sulfonylurea. The miR-23a levels were higher in diabetic participants than in nondiabetic controls.

Keyword

Biomarkers; Diabetic nephropathies; Exosomes; MicroRNAs; Type 2 diabetes mellitus
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