Preventative effects of resveratrol and estradiol on streptozotocin-induced diabetes in ovariectomized mice and the related mechanisms

PLoS One. 2018 Oct 1;13(10):e0204499. doi: 10.1371/journal.pone.0204499. eCollection 2018.

Abstract

Resveratrol, a non-flavonoid polyphenolic compound, is structurally and functionally similar to estrogen and has drawn great attention for its potentially beneficial effects on diabetes. However, it is not known whether it shares the same protective effect against diabetes as estrogen and the underlying mechanisms. The aim of the present study was to investigate the protective effects of phytoestrogen resveratrol and exogenous 17β-estradiol against streptozotocin (STZ)-induced type 1 diabetes. Female mice were ovariectomized (OVX) and chronically injected with different concentrations of resveratrol (0.1, 1 or 10 mg/kg) and 17β-estradiol (0.01, 0.1 or 1 mg/kg) subcutaneously for 4 weeks, and the levels of blood glucose, plasma insulin, plasma antioxidant capacity, the changes of pancreatic islet cells and the expressions of glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS-1) and phosphorylation of extracellular signal-regulated kinase (p-ERK) were detected. Resveratrol and 17β-estradiol significantly inhibited the increase of the blood glucose level and the rise of plasma malondialdehyde in STZ-induced diabetic mice, improved the levels of plasma antioxidant capacity and plasma insulin, protected the pancreatic islet cells, and increased the expressions of GLUT4 and IRS-1, but decreased p-ERK expression in skeletal muscle and myocardial tissue. The results suggest that resveratrol or 17β-estradiol shows obvious protection against STZ-induced diabetes in OVX mice, the mechanisms probably involve their ameliorating antioxidant activities and islet function, promoting muscle glucose uptake and inhibiting the expression of p-ERK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Dose-Response Relationship, Drug
  • Estradiol / pharmacology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fasting / blood
  • Female
  • Gene Expression Regulation / drug effects
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Insulin / blood
  • Insulin Receptor Substrate Proteins / metabolism
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / pathology
  • Malondialdehyde / blood
  • Mice
  • Ovariectomy*
  • Phosphoproteins / metabolism
  • Resveratrol / pharmacology*

Substances

  • Antioxidants
  • Blood Glucose
  • Glucose Transporter Type 4
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Phosphoproteins
  • Estradiol
  • Malondialdehyde
  • Extracellular Signal-Regulated MAP Kinases
  • Resveratrol

Grants and funding

Funding was provided by the Administration of Traditional Chinese Medicine of Gansu Province (grant # GZK-2015-238) to HL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.