Macrophage Phenotype and Function: Effects of Islet Hormone Signaling
Janice Pang
Pinetree Secondary
Floor Location : S 004 H

Type 2 diabetes (T2D) is a chronic disease brought about by metabolic events such as insulin resistance and progressive impairments in the function of insulin-secreting β-cells. Recently, inflammation has been shown to impair insulin action in tissues and contribute to β-cell dysfunction in T2D. Another feature of T2D is an increased number of proinflammatory macrophages infiltrating pancreatic islets. Despite the close proximity of islet macrophages to high concentrations of islet hormones, studies have yet to investigate the effects of various islet hormones on macrophage function. Moreover, the polarization of macrophages has yet to be thoroughly defined in T2D. In this study, bone marrow-derived macrophages (BMDMs) were treated with insulin or glucagon for 21 h to determine whether macrophages express receptors for islet hormones and the effects of islet hormone receptor signalling on macrophage polarization. Results from RT-PCR revealed that BMDMs expressed mRNA for insulin and glucagon receptors. Insulin had no effect on the mRNA expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor, and the anti-inflammatory cytokines interleukin-10, and interleukin 1 receptor antagonist. Thus, insulin may not have an effect on macrophage phenotype and function. Conversely, 10^-7 M glucagon significantly increased mRNA expression of tumor necrosis factor. Therefore, low-dose glucagon may drive macrophages towards an M1 class. These data uncover potential effects of glucagon on macrophage polarization. Notably, a better understanding of the effects of islet hormones on macrophage phenotype and function can potentially lead to future studies investigating the effectiveness of targeting islet hormone signalling in T2D.