title: Exendin-4 improves resistance to Listeria monocytogenes infection in diabetic db/db mice.
abstract: The incidence of diabetes mellitus is increasing among companion animals. This disease has similar characteristics in both humans and animals. Diabetes is frequently identified as an independent risk factor for infections associated with increased mortality. In the present study, homozygous diabetic (db/db) mice were infected with Listeria (L.) monocytogenes and then treated with the anti-diabetic drug exendin-4, a glucagon-like peptide 1 analogue. In aged db/db mice, decreased CD11b(+) macrophage populations with higher lipid content and lower phagocytic activity were observed. Exendin-4 lowered high lipid levels and enhanced phagocytosis in macrophages from db/db mice infected with L. monocytogenes. Exendin-4 also ameliorated obesity and hyperglycemia, and improved ex vivo bacteria clearance by macrophages in the animals. Liver histology examined during L. monocytogenes infection indicated that abscess formation was much milder in exendin-4-treated db/db mice than in the control animals. Moreover, mechanistic studies demonstrated that expression of ATP binding cassette transporter 1, a sterol transporter, was higher in macrophages isolated from the exendin-4-treated db/db mice. Overall, our results suggest that exendin-4 decreases the risk of infection in diabetic animals by modifying the interaction between intracellular lipids and phagocytic macrophages.
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Hsien Yueh
authors.initials: HY
authors.lastname: Liu
authors.forename: Chih-Yao
authors.initials: CY
authors.lastname: Chung
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Yang
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Liang
authors.forename: Chi-Young
authors.initials: CY
authors.lastname: Wang
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Chang
authors.forename: Cicero Lee-Tian
authors.initials: CL
authors.lastname: Chang
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D001774:Blood Chemical Analysis; D002784:Cholesterol / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D050171:Dyslipidemias / Q000188:drug therapy / Q000235:genetics; D000077270:Exenatide; D005260:Female; D006943:Hyperglycemia / Q000188:drug therapy / Q000235:genetics; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D050356:Lipid Metabolism / Q000187:drug effects; D008089:Listeria monocytogenes / Q000187:drug effects* / Q000276:immunology; D008088:Listeriosis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000235:genetics; D010455:Peptides / Q000627:therapeutic use*; D010587:Phagocytosis / Q000187:drug effects; D014688:Venoms / Q000627:therapeutic use*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D002784:Cholesterol; D000077270:Exenatide