Role of Exercise mimicking drugs (EMDs) on macrophage polarization from M1 to M2 state
Type 2 diabetes (T2D) is now being considered as a pandemic disease due to its growing pervasiveness in the world population. Pathology of the disease is characterized by the presence of insulin resistance (IR), a major defect and early sign for the future development of T2D and is associated with a reduction in response to insulin induced uptake of glucose into specific tissues namely skeletal muscles and adipocytes. It is well established that obesity and sedentary lifestyle induces chronic low-grade inflammation in adipose tissue which is linked to the onset of insulin resistance further leading to the progression of T2D. There is a striking accumulation of macrophage population in adipose tissue of obese humans and prevention of macrophage infiltration is found to improve insulin sensitivity, which provides a possible link between IR and inflammation. Moreover studies have also revealed that adipose tissue macrophages of thin mice expressed numerous genes specific to M2 or “alternatively activated macrophages”, while in mice with induced obesity, overexpression of various pro-inflammatory genes typical of M1 or “classically activated macrophages” were observed. Fascinatingly, obesity leads to macrophage phenotypic switch from an M2 anti-inflammatory state to a pro-inflammatory M1 state in the adipose tissue which contributes to insulin resistance. Several studies indicate that exercise has many salutary effects on insulin sensitivity which strongly correlates the extent of physical activity with reduction in inflammatory response. However, the underlying mechanism still remains unclear. Based on the literature stated above, we have hypothesized that exercise could induce the expression of certain myokines/factors that promote insulin sensitivity. Thus we have made use of Exercise Mimicking Drugs (EMDs) to test the efficacy of these factors in ameliorating IR. It was observed that ionomycin effectively downregulates the LPS induced expression of pro-inflammatory genes like IL-6, TNF-α and MCP-1 in THP-1 cells while also enhancing the anti-inflammatory gene expression of IL-4.
Keywords: Insulin resistance, Inflammation, obesity, adipocytes