Altered Intestinal Permeability to Mannitol in Diabetes Mellitus Type I

Carratù, R.; Secondulfo, Mario; Magistris, Laura de; Iafusco, Dario; A, Urio; Carbone, Maria Grazia; Pontoni, Gabriele; Cartenì, M.; Prisco, Francesco

doi:10.1097/00005176-199903000-00010

Cited by 106 publications

(83 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These findings confirm the previous observation of abnormal intestinal permeability in patients with type 1 diabetes [5,6] and indicate the paracellular route as the site of a damaged passive transport across the intestinal barrier. This observation is in accord with a recent report showing in patients with type 1 diabetes and some of their relatives an increased concentration of circulating zonulin, a putative modulator of intestinal permeability, possibly acting on intercellular tight junctions [7].…”

Section: Discussionsupporting

confidence: 92%

“…More recently, an enteropathy with similar characteristics has also been described in the non-obese diabetic mouse [4]. In patients with type 1 diabetes, increased intestinal permeability [5][6][7], intestinal biopsy-documented signs of enhanced immune activation [8], ultrastructural changes [9] and increased concentrations of circulating zonulin [7] have been shown. In the BB rat, these features, detectable before the onset of clinical diabetes, are thought to be related to the systemic immune disorder; in human type 1 diabetes the natural history and the pathogenetic implications of these alterations remain to be clarified.…”

Section: Introductionmentioning

confidence: 77%

See 1 more Smart Citation

Increased intestinal permeability precedes clinical onset of type 1 diabetes

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis Recent observations have shown subclinical intestinal abnormalities in human type 1 diabetes. Whether these are related to the pathogenetic process or secondary to the diabetes remains to be clarified. The aim of this study was to investigate this issue by examining intestinal permeability to sugars in subjects at different stages of type 1 diabetes: preclinical, new-onset and longterm established disease. Methods Eighty-one subjects with islet autoimmunity (18 preclinical, 28 new-onset and 35 long-term type 1 diabetes) and 40 healthy control subjects were investigated by a lactulose-mannitol test, consisting of oral administration of the two sugars and measurement of their urinary excretion.Results All groups of subjects with islet autoimmunity showed an increase in intestinal permeability (p≤0.009 vs controls) to the disaccharide lactulose, indicative of a damaged barrier, but a similar permeability to the monosaccharide mannitol (NS vs controls), indicative of an integral surface mucosa; consequently there was an increase in the lactulose:mannitol excretion ratio (p≤0.025 vs controls). Conclusions/interpretation These findings indicate the presence of a subclinical enteropathy associated with type 1 diabetes that is already detectable before clinical onset of the disease, and suggest that the small intestine is an organ participating in the pathogenetic process of type 1 diabetes.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 77%

Increased intestinal permeability precedes clinical onset of type 1 diabetes

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The intestinal surface barrier is one of the most important components of the innate immune system (Vaarala et al, 2008), whereby T1D compromises intestinal integrity (Carratù et al, 1999;Kuitunen et al, 2002;Sapone et al, 2006). Abnormalities of the intestinal barrier, the so-called 'leaky gut', expose the intestinal immune system to antigens in the setting of T1D (Vaarala et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Streptozotocin-induced type-1-diabetes disease onset in Sprague–Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity

et al. 2015

View full text Add to dashboard Cite

There is a growing appreciation that microbiota composition can significantly affect host health and play a role in disease onset and progression. This study assessed the impact of streptozotocin (STZ)-induced type-1-diabetes (T1D) on intestinal microbiota composition and diversity in Sprague-Dawley rats, compared with healthy controls over time. T1D was induced by injection of a single dose (60 mg STZ kg "1 ) of STZ, administered via the intraperitoneal cavity. Total DNA was isolated from faecal pellets at weeks 0 (pre-STZ injection), 1, 2 and 4 and from caecal content at week 5 from both healthy and T1D groups. High-throughput 16S rRNA sequencing was employed to investigate intestinal microbiota composition. The data revealed that although intestinal microbiota composition between the groups was similar at week 0, a dramatic impact of T1D development on the microbiota was apparent post-STZ injection and for up to 5 weeks. Most notably, T1D onset was associated with a shift in the Bacteroidetes : Firmicutes ratio (P,0.05), while at the genus level, increased proportions of lactic acid producing bacteria such as Lactobacillus and Bifidobacterium were associated with the later stages of T1D progression (P,0.05). Coincidently, T1D increased caecal lactate levels (P,0.05). Microbial diversity was also reduced following T1D (P,0.05). Principle co-ordinate analyses demonstrated temporal clustering in T1D and control groups with distinct separation between groups. The results provide a comprehensive account of how T1D is associated with an altered intestinal microbiota composition and reduced microbial diversity over time.

show abstract

“…Our group recently identified a wheat storage globulin-like protein as a candidate diabetes-related antigen in diabetic rats and human patients [4]. There is evidence that the gut is mildly inflamed and abnormally permeable to lumen antigens in BBdp rats [10][11][12][13][14] and in human patients with type 1 diabetes [15][16][17][18]. However, remarkably little is known about the immune state of the gut-associated lymphoid tissue (GALT) in animals or humans that spontaneously develop type 1 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Chakir¹,

Lefebvre

Wang³

et al. 2005

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis: Type 1 diabetes is the result of an inflammatory T helper 1 (Th1) lymphocyte-mediated beta cell destructive process. The majority of diabetesprone BioBreeding (BBdp) rats fed wheat protein-based diets, such as NTP-2000, develop type 1 diabetes and display a mild coeliac-like enteropathy. Mesenteric lymph nodes (MLNs), which drain the gut, are the major inductive site where dietary antigens are recognised in the gut-associated lymphoid tissue (GALT). We hypothesised that this compartment could be a site of abnormal wheat proteininduced Th1 cell activation. Methods: MLN cells were isolated from BBdp and BB control (BBc) rats that were fed NTP-2000 or a hydrolysed casein (HC)-based diet at ages that pre-date classic insulitis. The inflammatory status, phenotype and proliferation of these cells in response to wheat protein were determined. Results: The expression ratio of T-bet : Gata3, master transcription factors for Th1 and Th2 cytokines, was increased in the MLN from NTP-2000-fed BBdp rats compared with that from BBc rats, mainly due to decreased Gata3 expression. CD3 + CD4 + IFN-γ + T cells were more prevalent in the MLN of wheatfed BBdp rats, but remained at control levels in BBdp rats fed a diabetes-retardant HC diet. BBdp MLN cells proliferated in response to wheat protein antigens in a specific, dose-dependent manner, and >93% of cells were CD3 + CD4 + T cells. This proliferation was associated with a low proportion of CD4 + CD25 + T cells and a high proportion of dendritic cells in the MLN of BBdp rats. Conclusions/ interpretation: Before insulitis is established, the MLNs of wheat-fed BBdp rats contain an unusually high proportion of Th1 cells that proliferate specifically in response to wheat protein antigens.

show abstract

Altered Intestinal Permeability to Mannitol in Diabetes Mellitus Type I

Cited by 106 publications

References 30 publications

Increased intestinal permeability precedes clinical onset of type 1 diabetes

Increased intestinal permeability precedes clinical onset of type 1 diabetes

Streptozotocin-induced type-1-diabetes disease onset in Sprague–Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Contact Info

Product

Resources

About