miR-150 regulates glucose utilization through targeting GLUT4 in insulin-resistant cardiomyocytes

Acta Biochim Biophys Sin (Shanghai). 2020 Oct 19;52(10):1111-1119. doi: 10.1093/abbs/gmaa094.

Abstract

MicroRNAs (miRNAs) play an important role in cardiac function and metabolism. However, whether they regulate insulin resistance (IR) of cardiomyocytes remains unclear. The aim of the present study was to shed light on this issue with a focus on miR-150. We found here that miR-150 level was elevated in myocardium of type 2 diabetes mellitus (T2DM) rat model and in insulin-resistant cardiomyocytes induced by high glucose (25 mM) and high insulin (1 μM). Deregulation of miR-150 downregulated the protein and mRNA levels of glucose transporter 4 (GLUT4) as assessed by western blot, real-time polymerase chain reaction (qPCR), and immunofluorescence assays. Overexpression of miR-150 inhibited glucose utilization in cardiomyocytes as detected by 2-deoxyglucose transport and glucose consumption assays. In contrast, knockdown of miR-150 significantly increased glucose uptake in cardiomyocytes. Moreover, GLUT4 translocation was increased after transfection of miR-150 inhibitor (AMO-150). Collectively, miR-150 reduced glucose utilization by directly decreasing the expression and translocation of GLUT4 in the cardiomyocytes with IR and therefore might be a new therapeutic target for metabolic diseases such as T2DM.

Keywords: GLUT4; insulin resistance; miR-150; type 2 diabetes mellitus.

MeSH terms

  • Animals
  • Animals, Newborn
  • Biological Transport / genetics
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism
  • Glucose / metabolism
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism*
  • Heart / physiopathology
  • Insulin / metabolism
  • Insulin Resistance / genetics*
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Myocardium / cytology
  • Myocardium / metabolism
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / ultrastructure
  • Primary Cell Culture
  • Rats, Sprague-Dawley

Substances

  • Glucose Transporter Type 4
  • Insulin
  • MIRN150 microRNA, rat
  • MicroRNAs
  • Slc2a4 protein, rat
  • Glucose