Glucocorticoid exposure causes disrupted glucoregulation, cardiac inflammation and elevated dipeptidyl peptidase-4 activity independent of glycogen synthase kinase-3 in female rats

Arch Physiol Biochem. 2019 Dec;125(5):414-422. doi: 10.1080/13813455.2018.1479426. Epub 2018 Jun 18.

Abstract

Objective: We tested the hypothesis that glucocorticoid (GC) exposure in female rats would lead to glucose dysregulation and elevated cardiac inflammatory biomarkers, which are dipeptidyl peptidase-4 (DPP-4)- and glycogen synthase kinase-3 (GSK-3)-dependent. Methods: Female Wistar rats received vehicle (control; n = 6) or GC (dexamethasone; n = 6; 0.2 mg/kg; p.o.) for six days. Insulin resistance was determined by HOMA-IR. DPP-4 activity was determined by fluorescence method, whereas vascular cell adhesion molecule-1 (VCAM-1), uric acid, malondialdehyde (MDA), lactate dehydrogenase (LDH) and nitric oxide (NO) from plasma and cardiac homogenate were estimated as cardiac pro-inflammatory biomarkers. Results: Results showed that GC exposure resulted in glucose dysregulation and increased plasma and cardiac pro-inflammatory markers which are associated with elevated DPP-4 activity but reduced GSK-3. Conclusions: The present results demonstrate that GC exposure would cause glucose dysregulation, increased DPP-4 activity and cardiac inflammation that is independent of GSK-3.

Keywords: DPP-4; Dexamethasone; GSK-3; VCAM-1; glucose homeostasis.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Dipeptidyl Peptidase 4 / metabolism*
  • Female
  • Glucocorticoids / pharmacology*
  • Glucose / metabolism*
  • Glycogen Synthase Kinase 3 / metabolism
  • Heart / drug effects*
  • Inflammation / metabolism
  • Myocardium / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar

Substances

  • Biomarkers
  • Glucocorticoids
  • Glycogen Synthase Kinase 3
  • Dipeptidyl Peptidase 4
  • Glucose