EFFECT OF IN-VITRO AND IN-VIVO MODELS OF DIABETES ON AKT PATHWAY IN PERIPHERAL BLOOD LYMPHOCYTES

Keywords: Diabetes, glucose, palmitic acid, GSK3β, VDAC

Abstract

In this study, we investigated the effect of in-vitro and in-vivo models of diabetes on AKT phosphorylation and its downstream targets. For the in-vitro model, peripheral blood lymphocytes (PBL) were incubated with high glucose (Glc) or palmitic acid (PA) concentrations while for the in-vivo model, PBL was isolated from alloxan-induced diabetic mice. PBL was then examined for triglyceride content, lipid accumulation, enzyme activities, and phosphorylation state of AKT, glycogen synthase kinase-3β (GSK3β) and voltage-gated anion channel (VDAC). CD4/CD8 ratio and pro-inflammatory profile were monitored as indicators of lymphocyte function. Glc-/PA-exposed PBL demonstrated increased triglyceride content and lipid droplets. This was accompanied by increased acetyl CoA carboxylase and decreased carnitine palmitoyltransferase activity while glycogen synthase activity was unchanged. Glc- and PA-exposed PBL showed decreased pAKT-, pGSK3β-protein expression. Interestingly, relative to pVDAC expression, Glc- and PA-exposed PBL showed contrasting results. An altered CD4/CD8 ratio with elevated pro-inflammatory profile was noted indicating impaired lymphocyte function. Results of the in-vivo model were consistent with those of cultured PBL except the data of pVDAC expression showed resemblance to those of Glc-incubated PBL. These results demonstrate that diabetic conditions can reduce the expression of AKT and its downstream targets, GSK3β which might contribute to impaired lymphocyte function. Contrasting results on pVDAC expression under high Glc and PA suggests the possible involvement of other candidate substrates downstream to GSK3β.

Author Biography

Melinda Nongbet Sohlang, Melinda, North-Eastern Hill University, Shillong, Meghalaya, India-793022

Ph.D. Scholar,

Department of Biotechnology & Bioinformatics, 

North-Eastern Hill University, 

Shillong-793022

Meghalaya, India

Published
2021-09-17
How to Cite
Sohlang, M., & Majaw, S. (2021). EFFECT OF IN-VITRO AND IN-VIVO MODELS OF DIABETES ON AKT PATHWAY IN PERIPHERAL BLOOD LYMPHOCYTES. Journal of Applied Biological Sciences, 15(3), 294-309. Retrieved from http://jabsonline.org/index.php/jabs/article/view/807
Section
Articles