title: Cathelicidin Antimicrobial Peptide: A Novel Regulator of Islet Function, Islet Regeneration, and Selected Gut Bacteria.
abstract: Cathelicidin antimicrobial peptide (CAMP) is a naturally occurring secreted peptide that is expressed in several organs with pleiotropic roles in immunomodulation, wound healing, and cell growth. We previously demonstrated that gut Camp expression is upregulated when type 1 diabetes-prone rats are protected from diabetes development. Unexpectedly, we have also identified novel CAMP expression in the pancreatic β-cells of rats, mice, and humans. CAMP was present even in sterile rat embryo islets, germ-free adult rat islets, and neogenic tubular complexes. Camp gene expression was downregulated in young BBdp rat islets before the onset of insulitis compared with control BBc rats. CAMP treatment of dispersed islets resulted in a significant increase in intracellular calcium mobilization, an effect that was both delayed and blunted in the absence of extracellular calcium. Additionally, CAMP treatment promoted insulin and glucagon secretion from isolated rat islets. Thus, CAMP is a promoter of islet paracrine signaling that enhances islet function and glucoregulation. Finally, daily treatment with the CAMP/LL-37 peptide in vivo in BBdp rats resulted in enhanced β-cell neogenesis and upregulation of potentially beneficial gut microbes. In particular, CAMP/LL-37 treatment shifted the abundance of specific bacterial populations, mitigating the gut dysbiosis observed in the BBdp rat. Taken together, these findings indicate a novel functional role for CAMP/LL-37 in islet biology and modification of gut microbiota.
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Lynley D
authors.initials: LD
authors.lastname: Pound
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Patrick
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Chandra E
authors.initials: CE
authors.lastname: Eberhard
authors.affiliation: Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Walid
authors.initials: W
authors.lastname: Mottawea
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Wang
authors.affiliation: Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Turki
authors.initials: T
authors.lastname: Abujamel
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Vandenbeek
authors.affiliation: Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Stintzi
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada fscott@ohri.ca.
authors.forename: Fraser W
authors.initials: FW
authors.lastname: Scott
mesh_terms: D000368:Aged; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D054804:Cathelicidins / Q000494:pharmacology / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D064806:Dysbiosis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D020869:Gene Expression Profiling; D005856:Germ-Free Life; D005934:Glucagon / Q000819:agonists / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000819:agonists / Q000378:metabolism; D000078790:Insulin Secretion; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D008297:Male; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D011919:Rats, Inbred Strains; D012038:Regeneration / Q000187:drug effects*; D046509:Tissue Culture Techniques
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D054804:Cathelicidins; D005765:Gastrointestinal Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; C534394:cathelicidin LL-37 (18-29), human; D005934:Glucagon