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Non-Coding RNA in Type 2 Diabetes Cardio-Renal Complications and SGLT2 Inhibitor Response.

Elena Rykova1,2, Elena Shmakova3,4, Igor Damarov1

  • 1Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (IC&G SB RAS), Lavrentjev Prospect 10, 630090 Novosibirsk, Russia.

International Journal of Molecular Sciences
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PubMed
Summary
This summary is machine-generated.

Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) offer benefits beyond blood glucose control in type 2 diabetes mellitus (T2DM). This review explores how non-coding RNAs mediate SGLT2-i

Keywords:
SGLT2 inhibitorscardiac fibroblastscardiomyocyteschronic inflammationdiabetic cardiovascular complicationsdiabetic nephropathyendothelial cellsinnate immune cellsmacrophagesmesangial renal cellsncRNA genetic variantsnon-coding RNAs (ncRNAs)podocytessignaling pathwaystubular epithelial cellstype 2 diabetes mellitus

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Immunology

Background:

  • Type 2 diabetes mellitus (T2DM) involves hyperglycemia and insulin resistance, leading to inflammatory vascular complications.
  • Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) lower blood glucose and exhibit beneficial non-glycemic effects, including immune system modulation.
  • SGLT2 inhibitors show promise in reducing diabetic cardiomyopathy (DCM) and chronic kidney disease (CKD) risks, potentially via non-coding RNA pathways.

Purpose of the Study:

  • To review the role of non-coding RNAs (ncRNAs) in mediating the cardio-renal benefits of SGLT2 inhibitors in T2DM.
  • To explore the detection, genetics, and functional effects of ncRNAs in T2DM.
  • To highlight the involvement of ncRNAs in innate immune cell inflammatory responses influenced by SGLT2 inhibitors.

Main Methods:

  • Literature review focusing on ncRNAs (miRNAs, lncRNAs, circRNAs) and SGLT2 inhibitor mechanisms.
  • Analysis of RNA-sequencing data for constructing competitive endogenous RNA (ceRNA) networks.
  • Examination of ncRNA expression changes in T2DM pathogenesis and SGLT2 inhibitor action.

Main Results:

  • ncRNAs, including miRNAs, lncRNAs, and circRNAs, play a significant regulatory role in T2DM pathogenesis.
  • SGLT2 inhibitors exert cardio-renal protective effects through signaling pathways involving ncRNAs.
  • ncRNAs are implicated in the inflammatory responses of innate immune cells modulated by SGLT2 inhibitors.

Conclusions:

  • Non-coding RNAs are critical mediators of SGLT2 inhibitor efficacy in managing cardio-renal complications in T2DM.
  • Understanding ncRNA-mediated ceRNA networks can lead to novel diagnostic markers and therapeutic strategies for T2DM.
  • Targeting ncRNAs offers a promising avenue for enhancing the immune-modulatory and protective effects of SGLT2 inhibitors.