Vitamin D downregulates key genes of diabetes complications in cardiomyocyte

J Cell Physiol. 2019 Nov;234(11):21352-21358. doi: 10.1002/jcp.28743. Epub 2019 Jun 7.

Abstract

Objective: Vitamin D deficiency has been reported to be associated with the incidence of type 1 and type 2 diabetes and worsening of diabetes complications. This study was designed to investigate the effect of vitamin D treatment on the expression of five key genes involved in the development of diabetic cardiomyopathy.

Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups. The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin (STZ) to develop diabetes. Then groups were treated for 4 weeks either with placebo or vitamin D (two injections of 20,000 IU/kg). Serum levels of glucose, insulin, HbA1c, and advanced glycation end products (AGEs), as well as the gene expression of AGE cellular receptor (RAGE), glyoxalase, aldose reductase, O-GlcNAc transferase (OGT), and glutamine-fructose-6-phosphate aminotransferase (GFAT) and nuclear factor-kB (NF-kB) activity of nuclear extracts were assessed at the end of experiment.

Results: Increment in serum cholecalciferol could improve hyperglycaemia and hypoinsulinemia in diabetic rats. In addition, a significant reduction was observed in RAGE, OGT, and GFAT gene expression and NF-kB activity in cardiac myocytes.

Conclusions: Vitamin D might contribute in reducing diabetic cardiomyopathy not only by improving blood glucose and insulin levels but also via downregulating AGE and hexosamine pathways and decreasing NF-kB activity in heart tissue.

Keywords: O-GlcNAc transferase; advanced glycation end products; diabetes complications; diabetic cardiomyopathies; glutamine-fructose-6-phosphate transaminase; vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetic Cardiomyopathies / metabolism*
  • Down-Regulation
  • Male
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transcriptome / drug effects*
  • Vitamin D / pharmacology*

Substances

  • Vitamin D