Metformin, empagliflozin and their combination modulate ex-vivo macrophage inflammatory gene expression

Abstract

Type-2 Diabetes Mellitus is a complex, chronic illness characterized by persistent high blood glucose levels. Patients can be prescribed anti-diabetes drugs as single agents or in combination depending on the severity of their condition. Metformin and empagliflozin are two commonly prescribed anti-diabetes drugs which reduce hyperglycemia, however their direct effects on macrophage inflammatory responses alone or in combination are unreported. Here we show that metformin and empagliflozin elicit proinflammatory responses on mouse bone-marrow derived macrophages with single agent challenge, which are modulated when added in combination. In-silico docking experiments suggested that empagliflozin can interact with both TLR2 and DECTIN1 receptors and we observed that both empagliflozin and metformin increase expression of Tlr2 and Clec7a. Thus, findings from this study suggest that metformin and empagliflozin as single agents or in combination can directly modulate inflammatory gene expression in macrophages and upregulate the expression of their receptors.

Single-cell RNA sequencing of peripheral blood mononuclear cells reveals complex cellular signalling signatures of metformin treatment type 2 diabetes mellitus

“…SIGLEC14 enhanced TNF-alpha secretion and IL-1β release may play a role in inflammation. This effect is related to lipopolysaccharides and NLRP3 inflammasome [58–59]. In WGCNA network interaction results, TNFRSF1A is the most core genes.…”