Gene Expression of GSK3 in Type II Diabetics Compared to Non-Diabetics (ex vivo)

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.

Molecular mechanisms of skin wound healing in non-diabetic and diabetic mice in excision and pressure experimental wounds

“…AKT-pathway dysfunction in diabetic mice, which has been indicated as a possible cause of wound healing impairment (Huang et al 2015 ), is somewhat complex, involving AKT isoform switches, phosphorylation, and de-phosphorylation in the different phases of wound healing (coagulation, inflammation, proliferation, and remodeling) (Maurer et al 2014 ; Vines et al 2019 ; Jere et al 2019 ; Khorami et al 2020 ). A transient pharmacological activation of the PI3K-Akt-mTOR signaling axis has been considered a novel clinical intervention strategy to accelerate wound (ulcer) healing (Squarize et al 2010 ), and we recently demonstrated that the pro-healing effect of a mutated form of rhNGF includes Akt regulation (Giuliani et al 2020 ).…”