Intestinal Permeability in Diabetic Diarrhoea

Cooper, B. T.; Ukabam, S.O.; O'Brien, I.A.D.; Jw, Hare; Corrall, R. J. M.

doi:10.1111/j.1464-5491.1987.tb00828.x

Cited by 32 publications

(13 citation statements)

References 15 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Serum levels of D-LAC in diabetic mice were significantly higher than those in the control mice at 4 and 10 weeks, which indicated that the intestinal mechanical barrier was impaired and intestinal permeability had increased in diabetic mice. The results are consistent with previous reports (Cooper et al, 1987;Secondulfo et al, 2004;Brabletz et al, 2009). In investigation of the underlying mechanism for tight junction injury throughout the course of hyperglycemia, we found that the expression of tight junction proteins, namely Ocln and Zo1, were lower in diabetic mice (Figure 2).…”

Section: Discussionsupporting

confidence: 93%

Abnormal differentiation of intestinal epithelium and intestinal barrier dysfunction in diabetic mice associated with depressed Notch/NICD transduction in Notch/Hes1 signal pathway

Min

Qing

et al. 2014

Cell Biology International

View full text Add to dashboard Cite

Proliferative change and intestinal barrier dysfunction in intestinal mucosa of diabetes have been described, but the differentiation characteristics of intestinal epithelial cells (IECs) and the mechanisms in the IECs development remain unclear. To explore the intestinal epithelial constitution patterns and barrier function, the diabetic mouse model was induced by streptozotocin. Tight junctions between IECs were significantly damaged and the serum level of D-lactate was raised in diabetic mice (P < 0.05). The expression of Zo1 and Ocln in the small intestine of diabetic mice were lower, while the markers for absorptive cell (SI) and Paneth cell (Lyz1) were significantly higher than in control mice (P < 0.05). The expression of Msi1, Notch1, and Dll1 in small intestine gradually increased throughout the course of hyperglycemia in diabetic mice (P < 0.05). However, the expression of NICD, RBP-jκ, Math1, and Hes1 had a reverse trend compared with Msi1 and Notch1. Intestinal absorptive cells and Paneth cells had a high proliferation rate in diabetic mice. However, the intestinal barrier dysfunction associated with the decreased expressions of Zo1 and Ocln was detected throughout hyperglycemia. In conclusion, downregulation of Notch/Hes1 signal pathway caused by depressed Notch/NICD transduction is associated with the abnormal differentiation of IECs and intestinal barrier dysfunction in diabetic mice.

show abstract

Section: Discussionsupporting

confidence: 93%

Abnormal differentiation of intestinal epithelium and intestinal barrier dysfunction in diabetic mice associated with depressed Notch/NICD transduction in Notch/Hes1 signal pathway

Min

Qing

et al. 2014

Cell Biology International

View full text Add to dashboard Cite

show abstract

“…60 This has led to the suggestion that increased intestinal permeability attributable to alterations in intestinal TJs is responsible for the onset of T1D. 59,61,62 This hypothesis is supported by a recent study performed in an animal model that develops T1D spontaneously. 63 The authors of this study demonstrated increased permeability of the small intestine (but not of the colon) in BioBreeding diabetic-prone (BBDP) rats that preceded the onset of diabetes by at least a month.…”

Section: Type 1 Diabetes (T1d)supporting

confidence: 54%

Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation

Fasano

2008

The American Journal of Pathology

View full text Add to dashboard Cite

The anatomical and functional arrangement of the gastrointestinal tract suggests that this organ, beside its digestive and absorptive functions, regulates the trafficking of macromolecules between the environment and the host through a barrier mechanism. Under physiological circumstances, this trafficking is safeguarded by the competency of intercellular tight junctions, structures whose physiological modulation is mediated by, among others, the recently described protein zonulin. To prevent harm and minimize inflammation, the same paracellular pathway, in concert with the gut-associated lymphoid tissue and the neuroendocrine network, controls the equilibrium between tolerance and immunity to nonself antigens. The zonulin pathway has been exploited to deliver drugs, macromolecules, or vaccines that normally would not be absorbed through the gastrointestinal mucosal barrier. However, if the tightly regulated trafficking of macromolecules is jeopardized secondary to prolonged zonulin up-regulation, the excessive flow of nonself antigens in the intestinal submucosa can cause both intestinal and extraintestinal autoimmune disorders in genetically susceptible individuals. This new paradigm subverts traditional theories underlying the development of autoimmunity, which are based on molecular mimicry and/or the bystander effect, and suggests that the autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing intestinal barrier competency. Understanding the role of zonulin-dependent intestinal barrier dysfunction in the pathogenesis of autoimmune diseases is an area of translational research that encompasses many fields. The intestinal epithelium is the largest mucosal surface, providing an interface between the external environment and the mammalian host. Its exquisite anatomical and functional arrangements and the finely-tuned coordination of digestive, absorptive, motility, neuroendocrine, and immunological functions are testimonial of the complexity of the gastrointestinal (GI) system. Also pivotal is the regulation of molecular trafficking between the intestinal lumen and the submucosa via the paracellular space. The dimensions of the paracellular space are estimated to be between 10 and 15 Å, suggesting that under physiological circumstances, solutes with a molecular radius exceeding 15 Å (ϳ3.5 kDa) will be excluded from this uptake route. Macromolecule trafficking is dictated mainly by intestinal paracellular permeability, the regulation of which depends on the modulation of intercellular tight junctions (TJs). A century ago, TJs were conceptualized as a secreted extracellular cement forming an absolute and unregulated barrier within the paracellular space. The contribution of the paracellular pathway of the GI tract to the general economy of molecule trafficking between environment and host, therefore, was judged to be negligible. It is now apparent that TJs are extremely dynamic structures involved in several key functions of the intestinal epithe...

show abstract

“…However, more recent studies have shown that altered intestinal permeability occurs in T1D prior to the onset of complications (40,30), which is not the case in type 2 diabetes (145). This has led to the suggestion that an increased intestinal permeability due to alteration in intestinal TJ is responsible for the onset of T1D (40,37,118). This hypothesis is supported by studies performed in BioBreeding diabetic-prone (BBDP) rats that develop T1D spontaneously.…”

Section: Zonulin and Intestinal Barrier Functionmentioning

confidence: 99%

Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

Fasano

2011

Physiological Reviews

776

633

View full text Add to dashboard Cite

The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and to electrolytes and water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the finely tuned zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing the zonulin-dependent intestinal barrier function. This review is timely given the increased interest in the role of a “leaky gut” in the pathogenesis of several pathological conditions targeting both the intestine and extraintestinal organs.

show abstract

Intestinal Permeability in Diabetic Diarrhoea

Cited by 32 publications

References 15 publications

Abnormal differentiation of intestinal epithelium and intestinal barrier dysfunction in diabetic mice associated with depressed Notch/NICD transduction in Notch/Hes1 signal pathway

Abnormal differentiation of intestinal epithelium and intestinal barrier dysfunction in diabetic mice associated with depressed Notch/NICD transduction in Notch/Hes1 signal pathway

Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation

Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

Contact Info

Product

Resources

About