Involvement of Peroxisome Proliferator-Activated Receptor-a and g in Apelin Action on the Kidney in Type 2 Diabetic Rat Model

Abstract
Background: Apelin is an adipokine that revealed numerous
renoprotective actions; however, its effect in diabetic
nephropathy is controversial.
Aim of Study: The objectives of the current study were
to determine the action of apelin administration on nephropathy
in type 2 diabetic rat model and to clarify its possible mechanisms
and if PPARs activation is involved in these mechanisms.
Material and Methods: Thirty adult male wistar rats were
subdivided into control, diabetic and diabetic-apelin treated
rats. Type 2 diabetes was induced via a high-fat diet together
with a single low-dose of streptozotocin. Apelin was injected
intraperitoneally for 10 weeks. Serum glucose, insulin and
lipid profile were estimated. Homeostatic Model Assessment
for Insulin Resistance (HOMA-IR) was calculated. Renal
functions were evaluated by serum urea and creatinine, urinary
albumin excretion, urinary N-acetyl-beta-D-glucosaminidase
(NAG) activity and histopathological inspection. Renal tissue
homogenate was assessed for Superoxide Dismutase (SOD),
Malondialdehyde (MDA), Nitric Oxide (NO) content and
PPAR-a and PPAR-g gene expression.
Results: Apelin administration to diabetic rats improved
hyperglycemia, insulin resistance, dyslipidemia, renal function
parameters and pathological lesions in the kidney that resulted
from induction of diabetes. It elevates renal SOD and NO,
decreased MDA and increased PPAR-a and g gene expression
in comparison to diabetic rats.
Conclusions: Apelin administration to diabetic rats improved
insulin resistance, hyperglycemia, dyslipidemia and
renal functions which may be partially via its antioxidant
properties and NO dependent mechanism that struggled the
harmful properties of diabetes on the kidney. Besides, apelin
induced upregulation of both PPARa/g genes expression that
could be involved in the renoprotective effect of apelin. More
investigations for the mechanism by which apelin acts on
PPARa/g are recommended.