Superparamagnetic Iron Oxide Nanoparticles in Type 2 Diabetes: A Mechanistic Study on Metabolic Pathway Regulation and Mitochondrial Function

Dr. S. K. Patel, Dr. A. Dimitrov, Dr. L. Fernández, Dr. H. Okafor, Dr. M. Kowalczyk

Abstract:

Aim: Based on a previous study by our research group on superparamagnetic iron oxide
nanoparticles (SPIONs) the current study aimed to explore the antidiabetic effects of one and
two weekly doses of SPION-PEG-550 (22µmol Fe/Kg). The study focused on the metabolic
pathways that may mediate the antidiabetic actions of SPIONs-PEG in peripheral tissues
(skeletal muscle and kidney).
Methods: Diabetes was induced in 5-day neonatal rats with one dose of streptozotocin (70
mg/kg; n5-STZ rat model). At week 8, after confirmation of diabetes, rats were treated either
with one or two weekly doses of SPION-PEG-550 (22µmol Fe/Kg) for 4 weeks. Fasting
blood glucose level was monitored through the experiment. At the end of the study, rats
underwent oral glucose tolerance test, serum samples were collected for biochemical analysis
of insulin, adipocytokines, urea and creatinine. Muscles and kidneys were gathered to
measure the gene expression of several metabolic pathways and the corresponding protein
levels. Histopathology examination of muscle and pancreas was also performed.
Key finding: SPION-PEG-550 normalized the disturbed glucose homeostasis, reversed the
insulin resistance, and adjusted the serum level of different adipocytokines. It modulated the
insulin receptor substrates (IRS-1 and -2), improved several disturbed downstream effectors
of the insulin signaling (AMPK and mTOR) and Wnt pathway. Besides, it normalized
mitochondrial DNA copy number in both muscle and kidney. Histological examination of the
muscle and pancreas has shown almost normal functional characteristics. Two doses of
SPION-PEG-550/week have shown higher effectiveness but mild disturbed kidney function.
Significance: To our knowledge, this is the first study to examine the effect of SPIONs-PEG
on signaling pathways in the muscle and kidney of diabetic rats.