Metformin, Empagliflozin, and Their Combination Modulate Ex-Vivo Macrophage Inflammatory Gene Expression.
Adittya ArefinMatthew C GagePublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- gene expression
- glycemic control
- blood glucose
- type diabetes
- poor prognosis
- toll like receptor
- dna methylation
- cardiovascular disease
- end stage renal disease
- inflammatory response
- immune response
- adipose tissue
- oxidative stress
- ejection fraction
- molecular dynamics
- metabolic syndrome
- prognostic factors
- mesenchymal stem cells
- molecular dynamics simulations
- peritoneal dialysis
- insulin resistance
- molecular docking
- small molecule
- weight loss
- skeletal muscle
- long non coding rna