Interactive effects of apelin, renin-angiotensin system and nitric oxide in treatment of obesity-induced type 2 diabetes mellitus in male albino rats

Arch Physiol Biochem. 2019 Jul;125(3):244-254. doi: 10.1080/13813455.2018.1453521. Epub 2018 Mar 22.

Abstract

Apelin and its receptor (APJ) are involved in the regulation of a variety of pathophysiological processes. We studied the effect of apelin treatment on obesity-induced type 2 diabetes mellitus (T2DM) and possible interaction between apelin/APJ system and renin-angiotensin system (RAS). Forty eight male albino rats were divided into two groups: control group and diabetic group. Diabetic group was subdivided into: control diabetic, apelin-treated, apelin + losartan-treated, apelin + l-NAME-treated and losartan-treated diabetic subgroup. Administration of apelin-13 yielded an improvement of IR, dyslipidaemia, inflammation, oxidative stress with significant decrease in AT1R gene expression and significant increase in ACE2 gene expression in adipose tissues. Losartan + apelin yielded a further significant decrease in ATR1 gene expression, glycaemic indices, serum TGs and TPA versus Apelin only. Adding l-NAME in subgroup (2D) reversed the effect of apelin. We suggested that the beneficial effect of Apelin is mainly mediated by NO-activated pathway and/or ACE2/Ang (1-7) dependent pathway.

Keywords: Type 2 diabetes mellitus (T2DM); apelin; endothelial nitric oxide synthase (eNOS); renin–angiotensin system (RAS).

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Animals
  • Apelin / administration & dosage*
  • Biomarkers / analysis*
  • Blood Glucose / analysis
  • Diabetes Mellitus, Experimental / etiology
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Diet, High-Fat / adverse effects
  • Drug Therapy, Combination
  • Enzyme Inhibitors / administration & dosage
  • Insulin / metabolism
  • Insulin Resistance
  • Losartan / administration & dosage
  • Male
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • Nitric Oxide / metabolism*
  • Obesity / complications*
  • Obesity / etiology
  • Obesity / pathology
  • Rats
  • Renin-Angiotensin System / drug effects*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Apelin
  • Biomarkers
  • Blood Glucose
  • Enzyme Inhibitors
  • Insulin
  • Nitric Oxide
  • Losartan
  • NG-Nitroarginine Methyl Ester