title: Gliadin fragments and a specific gliadin 33-mer peptide close KATP channels and induce insulin secretion in INS-1E cells and rat islets of langerhans.
abstract: In non-obese diabetic (NOD) mice, diabetes incidence is reduced by a gluten-free diet. Gluten peptides, such as the compound gliadin, can cross the intestinal barrier and may directly affect pancreatic beta cells. We investigated the effects of enzymatically-digested gliadin in NOD mice, INS-1E cells and rat islets. Six injections of gliadin digest in 6-week-old NOD mice did not affect diabetes development, but increased weight gain (20% increase by day 100). In INS-1E cells, incubation with gliadin digest induced a dose-dependent increase in insulin secretion, up to 2.5-fold after 24 hours. A similar effect was observed in isolated rat islets (1.6-fold increase). In INS-1E cells, diazoxide reduced the stimulatory effect of gliadin digest. Additionally, gliadin digest was shown to decrease current through KATP-channels. A specific gliadin 33-mer had a similar effect, both on current and insulin secretion. Finally, INS-1E incubation with gliadin digest potentiated palmitate-induced insulin secretion by 13% compared to controls. Our data suggest that gliadin fragments may contribute to the beta-cell hyperactivity observed prior to the development of type 1 diabetes.
authors.affiliation: The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark. mortendall1988@gmail.com
authors.forename: Morten
authors.initials: M
authors.lastname: Dall
authors.forename: Kirstine
authors.initials: K
authors.lastname: Calloe
authors.forename: Martin
authors.initials: M
authors.lastname: Haupt-Jorgensen
authors.forename: Jesper
authors.initials: J
authors.lastname: Larsen
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitt
authors.forename: Knud
authors.initials: K
authors.lastname: Josefsen
authors.forename: Karsten
authors.initials: K
authors.lastname: Buschard
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D003981:Diazoxide / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D005903:Gliadin / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D054086:KATP Channels / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D008970:Molecular Weight; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D054086:KATP Channels; D053594:Myeloid Differentiation Factor 88; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D005903:Gliadin; D003981:Diazoxide