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Abstract
Restoration of the normoglycemic state is the basic tenet of diabetes research. Nowadays, using nanoemulsion drug delivery systems represent an alternative effective tool in Type 2 diabetes mellitus management. We aimed to investigate the anti-diabetic potential of metformin nanoemulsion and mesenchymal stem cells (MSCs) therapy on streptozotocin (STZ)-induced diabetic rat model. Nanoemulsion formulation was prepared with oil phase (5%v/v), 1gm metformin with a hydrophilic surfactant, then characterized for particle size and zeta potential.Adult male albino rats were induced for diabetes with 60 mg/kg STZ and were classified into 4 groups: STZ control group; STZ+MET group (orally administered daily dose of metformin 18 mg/200 g b.wt.); STZ+MSCs group (mono-therapeutic dose of BM-MSCs 1×106 cells/rat) and STZ+Nano-MET group (daily intraperitoneal dose of metformin nanoemulsion 18 mg/kg b.wt.). After 8 weeks, relative expression levels of hepatic IRS-1, AKT, Bcl-2, and Bax were assessed by qPCR. Also, histopathological investigations were performed. We reported cytoplasmic vacuolation, tissue necrosis, dilated blood sinusoid and congested hepatic vein in STZ group. Experimental animals either treated with metformin nanoemulsion or the mono-therapeutic dose of MSCs exhibited significant up-regulation in IRS-1/AKT pathway and Bcl-2 gene expression levels, as well as significant repression in Bax mRNA levels, besides a remarkable amelioration in a hepatic histological organization.Conclusion: Nano-MET holds an anti-diabetic potential that clearly surpasses metformin via affecting the insulin signaling pathway and apoptotic gene expression.
Highlights
The incidence of diabetes in North Africa/Middle East was 39 million in 2017, 55 million in 2019 (International Diabetes Federation, 2019) and it will upsurge to 82 million by 2045
We aimed to investigate the anti-diabetic potential of Keywords: metformin nanoemulsion and mesenchymal stem cells (MSCs) therapy on Nanoemulsion, diabetes, metformin, MSCs, apoptosis, insulin receptor substrate (IRS)/AKT pathway streptozotocin (STZ)-induced diabetic rat model
We evaluate the effect of MET nanoemulsion and MSCs therapy versus the oral administration of MET on the streptozotocin-induced diabetic rat model
Summary
The incidence of diabetes in North Africa/Middle East was 39 million in 2017, 55 million in 2019 (International Diabetes Federation, 2019) and it will upsurge to 82 million by 2045. T2DM accounts for the vast majority of diabetes cases for around 90%. Type 2 diabetes mellitus affects the vital roles of the liver in maintaining glucose homeostasis and controlling the levels of glucose release, giving rise to hyperglycemia. The binding of insulin to its receptor(White, 2002), brings about tyrosine phosphorylation of insulin receptor substrate (IRS), which activates IRS and allows its binding to phosphoinositide 3- kinase (PI3K). Protein kinase B (PKB or AKT) represents the main target of PI3K in hepatic cells and plays a key role in glucose uptake. PI3K activates AKT and triggers the translocation of intracellular GLUT4 vesicles to the plasma membrane. Once docked at the plasma membrane, GLUT4 begins glucose uptake, improves glucose utilization as well as, reduces serum glucose levels(Bertrand et al, 2008)
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