Insulin has a critical role in regulation of glucose uptake and metabolism in different tissues via activating of the tyrosine kinase signaling pathway [
1]. Insulin resistance (IR) as the main hyperglycemic process in non-insulin dependent diabetes mellitus (NIDDM) is observed in many tissues such as adipose and skeletal muscle [
2]. Alpha-synuclein (SNCA, α-Syn) as one of the members of synuclein protein family is mainly expressed in brain tissue. Synucleins have 127–140 amino acids with similar domains and sequence similarity of 62–55% [
3,
4]. SNCA as a principal component of Lewy bodies can be associated with neurodegenerative disorders such as Parkinson’s disease [
5,
6]. However, it has been shown that the SNCA is expressed not only in neurons but also in various tissues including liver, spleen, kidney, red blood cells, cardiomyocytes, and skeletal muscles [
7]. SNCA increases the glucose uptake in adipocytes and skeletal myocytes via activation of LPAR2/Gab1/PI3K/Akt signaling pathway and can be involved in prevention of insulin resistance [
1,
3,
8]. Moreover, SNCA increases the transfer of vesicles containing GLUT4 to the dopaminergic neurons cell surface through its interaction with Rab8 [
9]. It has reported that decreased levels of plasma alpha-synuclein were associated with insulin resistance. Furthermore, the plasma level of alpha-synuclein was reversely related to body mass index (BMI) and homeostatic model assessment for insulin resistance (HOMA-IR) [
1]. However, there is not any clear principal mechanism of SNCA interactions with molecules in the insulin-dependent intracellular pathway. Since the basal expression of
SNCA in the muscle cells in response to insulin has not been investigated to date, we decided to examine the expression of
SNCA in insulin-resistant (IR) and insulin-sensitive (IS) models of skeletal muscle cells in both in vitro and in vivo studies.