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.
Highlights
Gluten is a wheat protein that confers elasticity to white bread, and it is universally present in the western diet
Gliadin digest induces weight gain in non-obese diabetic (NOD) mice and acutely lowers blood glucose levels In NOD mice, we observed no change in blood glucose levels (Fig. 1A) or diabetes incidence (Fig. 1B) after six gliadin digest injections from the mice were 6 weeks old
The effect of gliadin digest was independent of glucose, as stimulation in the presence of 3 mM glucose led to an increase in insulin secretion by 1.760.4 fold (Fig. 2C, P = 0.01, n = 4)
Summary
Gluten is a wheat protein that confers elasticity to white bread, and it is universally present in the western diet. Gliadin is a strongly hydrophobic glycoprotein, with a very poor solubility. This severely limits its enzymatic degradation, which results in the persistence of gliadin fragments in the gut and intestine. This has been reported to initiate subclinical inflammation in the intestinal mucosa [1]. Up to 2% of Caucasians develop celiac disease, known as gluten intolerance, which is an immune-mediated enteropathy. A gliadin 19-mer has been described as a gliadin digestion product, and transport of the 19-mer across the epithelial barrier is well-established in untreated celiac disease patients [3]. Patients with type 1 diabetes mellitus (T1D) have increased intestinal permeability [5], which suggests that gluten exposure may be increased in this group
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