title: Oral insulin (human, murine, or porcine) does not prevent diabetes in the non-obese diabetic mouse.
abstract: Studies have shown oral insulin prevents type 1 diabetes (T1D) in mouse models, however human trials were inconclusive. We tested the ability of different insulins to prevent T1D in non-obese diabetic mice. Mice received oral insulin or PBS twice weekly and disease was monitored. Contrary to previous studies, no insulin tested showed significant ability to prevent T1D, nor did testing of linked suppression in a delayed type hypersensitivity model have reproducible effect. To investigate delivery of antigen within the GI tract, blue dye was fed to mice. Dye traveled 5-8 cm from stomach to small intestine within 10s, suggesting orally administered antigen may not get digested in the stomach in mice. Insulin incubated with jejunum extracts was instantly digested. Thus, in humans large doses of insulin may be required to achieve tolerance as antigen may be more vulnerable to digestion in the stomach even before reaching the small intestine.
authors.affiliation: Type 1 Diabetes R&D Center, Novo Nordisk Research Center, Seattle, WA, USA.
authors.forename: Minh N
authors.initials: MN
authors.lastname: Pham
authors.affiliation: Type 1 Diabetes R&D Center, Novo Nordisk Research Center, Seattle, WA, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Gibson
authors.affiliation: Type 1 Diabetes R&D Center, Novo Nordisk Research Center, Seattle, WA, USA.
authors.forename: Anna K E
authors.initials: AK
authors.lastname: Rydén
authors.affiliation: Type 1 Diabetes R&D Center, Novo Nordisk Research Center, Seattle, WA, USA.
authors.forename: Nikole
authors.initials: N
authors.lastname: Perdue
authors.affiliation: Type 1 Diabetes R&D Center, Novo Nordisk Research Center, Seattle, WA, USA.
authors.forename: Tamar E
authors.initials: TE
authors.lastname: Boursalian
authors.affiliation: Type 1 Diabetes R&D Center, Novo Nordisk Research Center, Seattle, WA, USA; Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Philippe P
authors.initials: PP
authors.lastname: Pagni
authors.affiliation: Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Ken
authors.initials: K
authors.lastname: Coppieters
authors.affiliation: Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Skonberg
authors.affiliation: Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Porsgaard
authors.affiliation: Type 1 Diabetes R&D Center, Novo Nordisk Research Center, Seattle, WA, USA; Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: von Herrath
authors.affiliation: Type 1 Diabetes R&D Center, Novo Nordisk Research Center, Seattle, WA, USA. Electronic address: jvl@novonordisk.com.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Vela
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000276:immunology; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007108:Immune Tolerance; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D013552:Swine
chemical_list: D000941:Antigens; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin
keywords: Insulin; Mouse models; NOD; Oral tolerance; Type 1 diabetes