Abstract

In the current study, we developed resveratrol (RES)-loaded solid lipid nanoparticle (SLN-RES) in order to improve insulin resistance through the upregulation of SNARE protein complex in rats with type 2 diabetes. The SLN-RES characteristics include the following: the average size of 248 nm, the zeta potential of − 16.5 mV, and 79.9% RES entrapment efficiency. The release profile of SLN-RES showed an initial burst followed by a sustained release in natural condition. Infrared spectroscopy results revealed good incorporation of RES into core SLN. Spherical nanoparticle with less aggregation was observed under electronic microscopic examination. Oral administration of SLN-RES prevented weight loss and showed better hypoglycemic effect than RES. Serum oxidative stress status was restored to the normal level by SLN-RES. Furthermore, expression of synaptosomal-associated protein 23 (Snap23), syntaxin-4 (Stx4), and vesicle-associated membrane protein 2 (Vamp2) as the major elements of SNARE protein complex were reduced by SLN-RES more significantly than RES treatment in muscle tissue. However, SLN-RES has a similar effect to RES treatment in adipose tissue. Taken together, our results revealed SLN-RES could be a modern and interestingly therapeutic approach for the improvement of insulin resistance through targeting the expression of Snap23, Stx4, and Vamp2 in adipose and muscle tissues.

Highlights

  • Type 2 diabetes mellitus is a metabolic disorder that is characterized by insulin resistance

  • We investigated the effect of oral administration of Solid lipid nanoparticle (SLN)-RES on the gene expression of synaptosomal-associated protein 23 (Snap23), Stx4, and vesicle-associated membrane protein 2 (Vamp2) in adipose and muscle tissue

  • Physicochemical Characterization of Resveratrol-loaded solid lipid nanoparticle (SLN-RES) As can be seen in Table 1, as the drug to lipid ratio increased, the particle size and polydispersity index (PDI) value were almost constant which could be due to the formation of multiple phospholipid layers in SLN [11]

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Summary

Introduction

Type 2 diabetes mellitus is a metabolic disorder that is characterized by insulin resistance. Research attempt by Côté et al showed the acute intraduodenal infusion of RES compensated insulin resistance via decreasing duodenal SIRT1 protein and reducing hepatic glucose production in the rat model [4]. It is Gencoglu et al reported the intraperitoneal administration of RES relieved insulin resistance in diabetic rats via normalizing the expression of visfatin and upregulating the SIRT1 expression in skeletal muscle. RES feeding leads to increase GLUT4 and GLUT2 expression in streptozotocin-induced diabetes in rats Overall, these findings provided novel insights into the beneficial effects of RES supplementation against insulin resistance. Despite its promising therapeutic application, low intestinal absorption and gastrointestinal degradation mainly lead to low bioavailability of RES when administered orally [7]

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