title: Insulin treatment directly restores neutrophil phagocytosis and bactericidal activity in diabetic mice and thereby improves surgical site Staphylococcus aureus infection.
abstract: Bacterial infections, including surgical site infections (SSI), are a common and serious complication of diabetes. Staphylococcus aureus, which is eliminated mainly by neutrophils, is a major cause of SSI in diabetic patients. However, the precise mechanisms by which diabetes predisposes to staphylococcal infection are not fully elucidated. The effect of insulin on this infection is also not well understood. We therefore investigated the effect of insulin treatment on SSI and neutrophil function in diabetic mice. S. aureus was inoculated into the abdominal muscle in diabetic db/db and high-fat-diet (HFD)-fed mice with or without insulin treatment. Although the diabetic db/db mice developed SSI, insulin treatment ameliorated the infection. db/db mice had neutrophil dysfunction, such as decreased phagocytosis, superoxide production, and killing activity of S. aureus; however, insulin treatment restored these functions. Ex vivo treatment (coincubation) of neutrophils with insulin and euglycemic control by phlorizin suggest that insulin may directly activate neutrophil phagocytic and bactericidal activity independently of its euglycemic effect. However, insulin may indirectly restore superoxide production by neutrophils through its euglycemic effect. HFD-fed mice with mild hyperglycemia also developed more severe SSI by S. aureus than control mice and had impaired neutrophil phagocytic and bactericidal activity, which was improved by insulin treatment. Unlike db/db mice, in HFD mice, superoxide production was increased in neutrophils and subsequently suppressed by insulin treatment. Glycemic control by insulin also normalized the neutrophil superoxide-producing capability in HFD mice. Thus, insulin may restore neutrophil phagocytosis and bactericidal activity, thereby ameliorating SSI.
authors.affiliation: Department of General Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Yano
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujino
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Yoritsuna
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hiromi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Koji
authors.initials: K
authors.lastname: Hamada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ono
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iwaya
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
authors.forename: Shuhji
authors.initials: S
authors.lastname: Seki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D048909:Diabetes Complications / Q000188:drug therapy / Q000382:microbiology; D003920:Diabetes Mellitus / Q000276:immunology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D013530:Surgical Wound Infection / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D007328:Insulin