Format

Send to

Choose Destination
Clin Immunol. 2016 Mar;164:28-33. doi: 10.1016/j.clim.2016.01.013. Epub 2016 Jan 25.

Oral insulin (human, murine, or porcine) does not prevent diabetes in the non-obese diabetic mouse.

Author information

1
Type 1 Diabetes R&D Center, Novo Nordisk Research Center, Seattle, WA, USA.
2
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.
3
Novo Nordisk A/S, Måløv, Denmark.
4
Type 1 Diabetes R&D Center, Novo Nordisk Research Center, Seattle, WA, USA. Electronic address: jvl@novonordisk.com.

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.

KEYWORDS:

Insulin; Mouse models; NOD; Oral tolerance; Type 1 diabetes

PMID:
26821303
DOI:
10.1016/j.clim.2016.01.013
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center