Ameliorative effect of nicotine exposure on insulin resistance is accompanied by decreased cardiac glycogen synthase kinase-3 and plasminogen activator inhibitor-1 during oral oestrogen-progestin therapy

Arch Physiol Biochem. 2018 May;124(2):139-148. doi: 10.1080/13813455.2017.1369549. Epub 2017 Sep 3.

Abstract

Context: Cigarette smoking is considered to be a major risk factor for the development of diabetes and cardiovascular disease. Oestrogen-progestin combined oral contraceptive (COC) use has been associated with adverse cardiometabolic events.

Objective: We hypothesized that nicotine would ameliorate insulin resistance (IR) that is accompanied by decreased cardiac glycogen synthase kinase-3 (GSK-3) and plasminogen activator inhibitor-1 (PAI-1).

Methods: Female Wistar rats received (po) low-(0.1 mg/kg) or high-nicotine (1.0 mg/kg) with or without COC containing 5.0 µg levonorgestrel plus 1.0 µg ethinylestradiol daily for 8 weeks.

Results: Data showed that COC treatment or nicotine exposure led to IR, glucose deregulation, atherogenic dyslipidemia, increased corticosterone, aldosterone, cardiac and circulating GSK-3 values and PAI-1. However, these effects with the exception of corticosterone and aldosterone were ameliorated in COC + nicotine-exposed rats.

Conclusion: Amelioration of IR induced by COC treatment is accompanied by decreased circulating PAI-1, cardiac PAI-1 and GSK-3 instead of circulating aldosterone and corticosterone.

Keywords: Combined oral contraceptives; glycogen synthase kinase-3; insulin resistance; nicotine; pancreatic β-cell function.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Aldosterone / blood
  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / prevention & control
  • Contraceptives, Oral, Combined / adverse effects*
  • Contraceptives, Oral, Combined / antagonists & inhibitors
  • Corticosterone / blood
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Ethinyl Estradiol / adverse effects*
  • Ethinyl Estradiol / antagonists & inhibitors
  • Female
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / blood
  • Glycogen Synthase Kinase 3 / metabolism*
  • Heart / drug effects*
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Resistance*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Levonorgestrel / adverse effects*
  • Levonorgestrel / antagonists & inhibitors
  • Myocardium / enzymology
  • Myocardium / metabolism
  • Nicotine / administration & dosage
  • Nicotine / therapeutic use*
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / therapeutic use
  • Plasminogen Activator Inhibitor 1 / blood
  • Plasminogen Activator Inhibitor 1 / chemistry
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Prediabetic State / chemically induced
  • Prediabetic State / metabolism
  • Prediabetic State / pathology
  • Prediabetic State / prevention & control
  • Random Allocation
  • Rats, Wistar

Substances

  • Biomarkers
  • Contraceptives, Oral, Combined
  • Drug Combinations
  • Insulin
  • Nicotinic Agonists
  • Plasminogen Activator Inhibitor 1
  • Serpine1 protein, rat
  • ethinyl estradiol, levonorgestrel drug combination
  • Ethinyl Estradiol
  • Aldosterone
  • Levonorgestrel
  • Nicotine
  • Glycogen Synthase Kinase 3
  • Corticosterone