title: Decreased circulating lactoferrin in insulin resistance and altered glucose tolerance as a possible marker of neutrophil dysfunction in type 2 diabetes.
abstract: BACKGROUND
  Lactoferrin is an innate immune system protein with multiple beneficial health activities.
  
  
  OBJECTIVE
  To gain insight in the interaction between innate immune system and metabolic disturbances (obesity and insulin resistance), we investigated the relationship between circulating lactoferrin and chronic inflammation-associated insulin resistance according glucose tolerance status in Caucasian population.
  
  
  METHODS
  Circulating nonstressed lactoferrin (ELISA), metabolic variables, and inflammatory markers were measured in 229 men, 94 with normal (NGT) and 135 with altered glucose tolerance (AGT). Lactoferrin secretion by neutrophil was investigated in whole-blood culture (four young NGT subjects, four older NGT subjects, and four patients with type 2 diabetes) under microbial lipopolysaccharide (LPS) with IL-6 and rosiglitazone treatment. We also tested the lactoferrin action in THP-1 cells under LPS stimulus.
  
  
  RESULTS
  Circulating lactoferrin was significantly decreased in patients with AGT (431.5 +/- 187.5 vs. 493.5 +/- 238.9 ng/ml, P = 0.02). In addition, circulating lactoferrin was negatively associated with hyperglycemia and obesity measures and positively with insulin sensitivity. Lactoferrin was negatively related to inflammatory markers, especially in AGT subjects. In ex vivo experiments, we found a significant decrease in LPS-induced lactoferrin release from neutrophils in subjects with type 2 diabetes. IL-6 coincubation decreased LPS-induced lactoferrin release in NGT subjects (P < 0.001). Finally, rosiglitazone treatment led to increased lactoferrin secretion (398 +/- 193 vs. 280.1 +/- 104.9 ng/ml, P < 0.0001). Lactoferrin decreased nuclear factor-kappabeta activation and IL-6, IL-8, and macrophage chemoattractant protein-1 expression under LPS challenge.
  
  
  CONCLUSIONS
  Decreased circulating lactoferrin levels may play a role in chronic low level inflammation-associated insulin resistance.
authors: Section of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomédica de Girona, 17007 Girona, Spain.
authors: J M
authors: JM
authors: Moreno-Navarrete
authors: F J
authors: FJ
authors: Ortega
authors: J
authors: J
authors: Bassols
authors: W
authors: W
authors: Ricart
authors: J M
authors: JM
authors: Fernández-Real
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007781:Lactoferrin / Q000097:blood* / Q000378:metabolism; D016014:Linear Models; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D044465:White People
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D007781:Lactoferrin