Abstract
Background: GSK3 is a serine/threonine kinase that is involved in the storage of glucose into glycogen through the negative regulation of glycogen synthase. Defects in GSK3 and glycogen synthase function are early stages of the development of insulin resistance, which may cause impaired glycogen synthesis in Type II diabetes. Methods: In this cross-sectional study, the gene expression level of GSK3 from Type II diabetic and non-diabetic participants was compared via real-time RT-PCR. To investigate the relationships between GSK3 expression and indicators of insulin resistance, Pearson's correlation analysis was performed. To compare the differences between GSK3 expression levels based on BMI categories, one-way ANOVA was used. Results: Gene expression of GSK3 was slightly higher in diabetic participants compared to non-diabetics, but it was statistically insignificant. Also, no significant difference was found based on BMI categories in the two groups. No significant association between GSK3 expression and indicators of insulin resistance was observed in non-diabetic participants. There was only a positive significant correlation between GSK3 expression and FBS in diabetic participants. Conclusion: These results indicate that the regulation of GSK3 may occur at the translation level, as gene expression level was unaltered between diabetic and non-diabetic participants. Also, since circulating levels of both glucose and insulin regulate GSK3 activity, tissue specificity for the expression and post-translation regulations of GSK3 may exist, which cause hyperactivation or overexpression in some target tissues in diabetes. Furthermore, it is probable that glycogen synthase activity is also regulated by non-insulin mediated mechanisms like exercise or allosteric changes, independent of GSK3 expression.
Highlights
Impaired insulin regulation of glucose transport and utilization is associated with insulin-resistance and diabetes [1].Insulin-induced glycogen synthesis in elevated postprandial blood glucose levels is necessary to maintain glucose homeostasis and defective regulation of glycogen synthesis by insulin is an additional feature of the insulin-resistant condition [2]
Glycogen synthase kinase-3 (GSK3) plays the main role in phosphatase and tensin homolog (PTEN) phosphorylation, which acts as an antagonist factor of insulin signal transduction [13]
To understand more about the involvement of GSK3 in obesity and insulin resistance, the correlation between GSK3 gene expression level and BMI level was considered and no significant correlation was found. These results indicate that regulation of GSK3 may occur at the level of translation, as gene expression levels were unaltered between diabetic and non-diabetic as well as based on BMI categories or family history of diabetes
Summary
Impaired insulin regulation of glucose transport and utilization is associated with insulin-resistance and diabetes [1].Insulin-induced glycogen synthesis in elevated postprandial blood glucose levels is necessary to maintain glucose homeostasis and defective regulation of glycogen synthesis by insulin is an additional feature of the insulin-resistant condition [2]. The Open Diabetes Journal, 2020, Volume 10 31 phosphatidylinositol-3 kinase (PI3K) cascade, which is the main pathway involved in glucose transport and glycogen synthesis [3]. By this signaling axis, insulin stimulates phosphorylation of phosphoinositide-dependent serine-threonine protein kinase (AKT) and Glycogen synthase kinase-3 (GSK3), which increases and decreases their activities, respectively [4]. A specificity of GSK3 regulation is that it is constitutively activated [8]; the negative regulation of GSK3 through the PI3K/AKT pathway keeps GSK3 activity at low stages [9] Several disease conditions, such as insulin resistance, can break cellular homeostasis and lead to increased GSK3 activity [10]. Defects in GSK3 and glycogen synthase function are early stages of the development of insulin resistance, which may cause impaired glycogen synthesis in Type II diabetes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
