Reversal of dexamethasone induced insulin resistance by Apocynin in L6 myotubes and 3T3L1 adipocytes – a mechanistic approach

Abstract

Abstract Objective The current study aims to decipher the putative interaction between skeletal muscle and adipose tissue in response to apocynin (APO) mediated glucose uptake in Dexamethasone (DXM) induced insulin resistance. Methods The gene expression of the molecular markers pertaining to insulin signaling pathway including IRTK, IRS-1, PI3K and GLUT-4 along with adipogenic markers like PPARα and adiponectin were studied. The results from the study aided in understanding the molecular effects of apocynin favoring the investigation of the crosstalk among the 3T3-L1 adipocytes and L6 myotubes. Results After confirming 100 nM DXM was ideal for inducing insulin resistance without much alteration in cell viability. This is taken further for inducing insulin resistance in both the chosen cell lines. The gene expression of IRTK and IRS-1 was found to be increased in APO treated, DXM+APO treated cells and was found to be equivalent to that expressed in 100 nM insulin treated cells. In DXM+APO treated L6 myotubes and 3T3-L1 adipocytes, IRTK showed a 2- fold and 3.7-fold increase compared to control respectively. Whereas IRS-1 showed 2.3-fold and 3.5-fold increase in L6 myotubes and 3T3-L1 adipocytes respectively. In addition to this PI3K exhibited a 2.6-fold increase in L6 myotubes and 3.3-fold change in adipocytes. The maximum fold increase of 7.3 was exhibited by GLUT-4 in adipocytes while it showed a 2.8-fold increase in myotubes. The impact of apocynin on adipogenic markers were also analyzed and it was found that DXM+APO treated cells show 3.6-fold and 3.4-fold decrease in the expression of adiponectin and PPAR-α respectively in 3T3-L1 adipocytes. Conclusion The results substantiate that APO (1 μM) has both anti-diabetic effect in L6 myotubes along with anti-adipogenic properties in 3T3-L1 adipocytes.