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Cathelicidins positively regulate pancreatic β-cell functions.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2016 Feb; Vol. 30 (2), pp. 884-94. Date of Electronic Publication: 2015 Nov 02. - Publication Year :
- 2016
-
Abstract
- Cathelicidins are pleiotropic antimicrobial peptides largely described for innate antimicrobial defenses and, more recently, immunomodulation. They are shown to modulate a variety of immune or nonimmune host cell responses. However, how cathelicidins are expressed by β cells and modulate β-cell functions under steady-state or proinflammatory conditions are unknown. We find that cathelicidin-related antimicrobial peptide (CRAMP) is constitutively expressed by rat insulinoma β-cell clone INS-1 832/13. CRAMP expression is inducible by butyrate or phenylbutyric acid and its secretion triggered upon inflammatory challenges by IL-1β or LPS. CRAMP promotes β-cell survival in vitro via the epidermal growth factor receptor (EGFR) and by modulating expression of antiapoptotic Bcl-2 family proteins: p-Bad, Bcl-2, and Bcl-xL. Also via EGFR, CRAMP stimulates glucose-stimulated insulin secretion ex vivo by rat islets. A similar effect is observed in diabetes-prone nonobese diabetic (NOD) mice. Additional investigation under inflammatory conditions reveals that CRAMP modulates inflammatory responses and β-cell apoptosis, as measured by prostaglandin E2 production, cyclooxygenases (COXs), and caspase activation. Finally, CRAMP-deficient cnlp(-/-) mice exhibit defective insulin secretion, and administration of CRAMP to prediabetic NOD mice improves blood glucose clearance upon glucose challenge. Our finding suggests that cathelicidins positively regulate β-cell functions and may be potentially used for intervening β-cell dysfunction-associated diseases.<br /> (© FASEB.)
- Subjects :
- Animals
Antimicrobial Cationic Peptides genetics
Apoptosis genetics
Cell Line, Tumor
Dinoprostone genetics
Dinoprostone metabolism
ErbB Receptors genetics
ErbB Receptors metabolism
Interleukin-1beta genetics
Interleukin-1beta metabolism
Male
Mice
Mice, Inbred NOD
Mice, Knockout
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-2 metabolism
Rats
Rats, Wistar
bcl-Associated Death Protein genetics
bcl-Associated Death Protein metabolism
bcl-X Protein genetics
bcl-X Protein metabolism
Cathelicidins
Antimicrobial Cationic Peptides metabolism
Insulin-Secreting Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 30
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 26527065
- Full Text :
- https://doi.org/10.1096/fj.15-275826