The innate immune system can immediately respond to microorganism intrusion by helping to prevent further invasion.
Bactericidal/permeability-increasing protein (BPI) is a major constituent of neutrophils that possesses anti-inflammatory properties.
Inflammation is increasingly recognized as a component of the
metabolic syndrome. We hypothesized that the production of BPI could be linked to
insulin sensitivity and
glucose tolerance. We studied circulating BPI across categories of
glucose tolerance. We also studied whether these cross-sectional associations were of functional importance. For this reason, we investigated circulating bioactive
lipopolysaccharide and the effects of changing
insulin action-
after treatment with an
insulin sensitizer (
metformin)-on circulating BPI in subjects with
glucose intolerance. Finally, we tested whether a 3'-untranslated region (UTR) BPI polymorphism led to differences in BPI and
insulin action among nondiabetic subjects. Age- and BMI-adjusted circulating BPI was significantly lower among patients with
type 2 diabetes. Circulating BPI correlated negatively with fasting and postload
glucose and
insulin concentrations. In subjects with
glucose intolerance, BPI was also linked to BMI, waist-to-hip ratio, and age- and BMI-adjusted
insulin sensitivity. Bioactive
lipopolysaccharide was negatively correlated with circulating BPI (r = -0.57, P < 0.0001) and positively with plasma
lipopolysaccharide-binding protein (r = 0.54, P = 0.002). In parallel to improved
insulin sensitivity, plasma BPI significantly increased in the
metformin group but not in the placebo group. A 3'-UTR BPI polymorphism was simultaneously associated with plasma BPI concentration, waist-to-hip ratio, fasting and postload
insulin concentration, fasting plasma
triglycerides, and
insulin sensitivity. These findings suggest that this component of the innate immune system is associated with metabolic pathways.