Effects of miR-152-Mediated Targeting of SOCS3 on Hepatic Insulin Resistance in Gestational Diabetes Mellitus Mice

Am J Med Sci. 2021 Mar;361(3):365-374. doi: 10.1016/j.amjms.2020.06.032. Epub 2020 Jul 9.

Abstract

Background: The present study explored the effects of miR-152-mediated targeting of suppressor of cytokine signaling 3 (SOCS3) on hepatic insulin resistance (HIR) in mice with gestational diabetes mellitus (GDM). Healthy SPF C57BL/6J mice were selected to establish a GDM model.

Methods: Mice were divided into seven groups as follows: Normal group, Model group, NC-mimic group, miR-152 mimic group, NC-pcDNA3.0 group, pcDNA3.0-SOCS group, and miR-152 mimic + pcDNA3.0-SOCS3 group. The relationship between miR-152 and SOCS3 expression was analyzed by a dual-luciferase reporter system. Islet cell morphology and expression of miR-152 and SOCS3 mRNA and protein in the islet tissue were detected by hematoxylin and eosin (HE) staining, reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. Fasting blood glucose (FBG) level was measured by a glucose meter while triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and insulin levels were determined by an automatic biochemical analyzer. Insulin resistance index (HOMA-IR) was calculated by the formula FBG × FINS/22.5.

Results: The results showed that the levels of miR-152, SOCS3, FBG, fasting insulin (FINS), TG, and TC increased, and HDL-C content decreased in other groups as compared with those in the Normal group (all p < 0.05). Oral glucose tolerance test (OGTT), FBG, FINS, TG, TC, and HDL-C values showed an opposite trend in miR-152 mimic and pcDNA3.0-SOCS3 groups as compared with the Model group (all p < 0.05).

Conclusions: miR-152 can inhibit HIR in GDM mice by downregulating the expression of SOCS3.

Keywords: Gestational diabetes mellitus; Hepatic; Insulin resistance; Mir-152; SOCS3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes, Gestational / genetics*
  • Diabetes, Gestational / metabolism
  • Female
  • Insulin Resistance / genetics*
  • Liver / metabolism*
  • Male
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Pregnancy
  • Suppressor of Cytokine Signaling 3 Protein / genetics*
  • Suppressor of Cytokine Signaling 3 Protein / metabolism

Substances

  • MIRN152 microRNA, mouse
  • MicroRNAs
  • Socs3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein