Occupation with grain crops is associated with lower type 1 diabetes incidence:Registry-based case-control study

Intranasal administration of gliadin prevents autoimmune diabetes in non-obese diabetic mice. The current study was designed to investigate if bakers are intranasally exposed to gluten during work and whether occupation as baker is inversely associated with type 1 diabetes. Gliadin was measured in nasal swabs from eight bakers and butchers. The odds ratio of type 1 diabetes in selected profession groups was analysed in a registry-based case-control study with data from 1980 to 2010 derived from Statistics Denmark. The cohort included 1,210,017 Danish individuals, thereof 15,451 with type 1 diabetes (1.28%). Average nasal gliadin swab content after full working days was 6.3 μg (confidence interval (CI): 2.8 to 9.7) among bakers, while no nasal gliadin was detected among butchers. The odds ratio of type 1 diabetes was lower among bakers (OR = 0.57; CI: 0.52 to 0.62) and agriculture workers occupied with production of grains (OR = 0.65; CI: 0.56 to 0.75). Bakers had a lower odds ratio of type 1 diabetes, which potentially could be attributed to exposure of nasal mucosal gluten during work, as observed in this study. If other studies confirm the present observations, intranasal gliadin administration could possibly be an easy and safe approach for the prevention of type 1 diabetes in high-risk individuals or prediabetic subjects

Gluten-Free Diet Only during Pregnancy Efficiently Prevents Diabetes in NOD Mouse Offspring

Studies have documented that the pathogenesis of autoimmune diabetes is influenced by the intake of gluten. Aims. To investigate the importance of gluten exposure during pregnancy and the subsequent development of autoimmune diabetes in offspring. Methods. Nonobese diabetic mice were divided into 7 groups to receive combinations of gluten-free and standard diet before, during, or after pregnancy. Diabetes incidence in offspring was followed in each group (n=16–27) for 310 days. Insulitis score and intestinal expression of T-cell transcription factors (RT-QPCR) were evaluated in animals from the different diet groups. Results. If mothers were fed a gluten-free diet only during pregnancy, the development of autoimmune diabetes in offspring was almost completely prevented with an incidence reduction from 62.5% in gluten-consuming mice to 8.3% (p<0.0001) in the gluten-free group. The islets of Langerhans were less infiltrated (p<0.001) and the intestinal expression of RORγt (Th17) (p<0.0001) reduced in mice whose mothers were Gluten-free during pregnancy. Conclusion. A gluten-free diet exclusively during pregnancy efficiently prevents autoimmune diabetes development in offspring and reduces insulitis and intestinal expression of RORγt (Th17)

Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration

Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development. We orally and intravenously administered 33-mer and 19-mer gliadin peptide to NOD, BALB/c, and C57BL/6 mice and found that the peptides readily crossed the intestinal barrier in all strains. Several degradation products were found in the pancreas by mass spectroscopy. Notably, the exocrine pancreas incorporated large amounts of radioactive label shortly after administration of the peptides. The study demonstrates that, even in normal animals, large gliadin fragments can reach the pancreas. If applicable to humans, the increased gut permeability in prediabetes and type 1 diabetes patients could expose beta cells directly to gliadin fragments. Here they could initiate inflammation and induce beta cell stress and thus contribute to the development of type 1 diabetes

Polycomb Group Genes: Keeping Stem Cell Activity in Balance

Overexpression of Polycomb group genes is often associated with cancer development, whereas complete deletion results in loss of stem cell activity. New studies show that partial loss of function of Polycomb group genes enhances the activity of blood stem/progenitor cells

Hedonic Taste in Drosophila Revealed by Olfactory Receptors Expressed in Taste Neurons

Taste and olfaction are each tuned to a unique set of chemicals in the outside world, and their corresponding sensory spaces are mapped in different areas in the brain. This dichotomy matches categories of receptors detecting molecules either in the gaseous or in the liquid phase in terrestrial animals. However, in Drosophila olfactory and gustatory neurons express receptors which belong to the same family of 7-transmembrane domain proteins. Striking overlaps exist in their sequence structure and in their expression pattern, suggesting that there might be some functional commonalities between them. In this work, we tested the assumption that Drosophila olfactory receptor proteins are compatible with taste neurons by ectopically expressing an olfactory receptor (OR22a and OR83b) for which ligands are known. Using electrophysiological recordings, we show that the transformed taste neurons are excited by odor ligands as by their cognate tastants. The wiring of these neurons to the brain seems unchanged and no additional connections to the antennal lobe were detected. The odor ligands detected by the olfactory receptor acquire a new hedonic value, inducing appetitive or aversive behaviors depending on the categories of taste neurons in which they are expressed i.e. sugar- or bitter-sensing cells expressing either Gr5a or Gr66a receptors. Taste neurons expressing ectopic olfactory receptors can sense odors at close range either in the aerial phase or by contact, in a lipophilic phase. The responses of the transformed taste neurons to the odorant are similar to those obtained with tastants. The hedonic value attributed to tastants is directly linked to the taste neurons in which their receptors are expressed

Possible Prevention of Diabetes with a Gluten-Free Diet

Gluten seems a potentially important determinant in type 1 diabetes (T1D) and type 2 diabetes (T2D). Intake of gluten, a major component of wheat, rye, and barley, affects the microbiota and increases the intestinal permeability. Moreover, studies have demonstrated that gluten peptides, after crossing the intestinal barrier, lead to a more inflammatory milieu. Gluten peptides enter the pancreas where they affect the morphology and might induce beta-cell stress by enhancing glucose- and palmitate-stimulated insulin secretion. Interestingly, animal studies and a human study have demonstrated that a gluten-free (GF) diet during pregnancy reduces the risk of T1D. Evidence regarding the role of a GF diet in T2D is less clear. Some studies have linked intake of a GF diet to reduced obesity and T2D and suggested a role in reducing leptin- and insulin-resistance and increasing beta-cell volume. The current knowledge indicates that gluten, among many environmental factors, may be an aetiopathogenic factors for development of T1D and T2D. However, human intervention trials are needed to confirm this and the proposed mechanisms

Editorial: The gut-pancreas axis in type 1 diabetes - a focus on environmental factors.

Floyel T, Funda D, Dodero VI, Haupt-Jorgensen M. Editorial: The gut-pancreas axis in type 1 diabetes - a focus on environmental factors. Frontiers in Endocrinology . 2023;14: 1270297