Macrophages in Islet Destruction in Autoimmune Diabetes Mellitus

Burkart, Volker; Kolb, Hubert

doi:10.1016/s0171-2985(96)80025-8

Cited by 16 publications

(9 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, enteral feeding with a higher delivery of ethanol increased formation of both carbon-centered free radicals and 4-hydroxynonenal-modified proteins in the pancreas (Figs. [6][7][8]. These data are consistent with the hypothesis that oxidative stress is involved in the pathogenesis of early alcohol-induced pancreatic injury (see Fig.…”

supporting

confidence: 90%

Development of an animal model of chronic alcohol-induced pancreatitis in the rat

Kono¹,

Nakagami²,

Rusyn³

et al. 2001

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

This study was designed to develop an animal model of alcoholic pancreatitis and to test the hypothesis that the dose of ethanol and the type of dietary fat affect free radical formation and pancreatic pathology. Female Wistar rats were fed liquid diets rich in corn oil (unsaturated fat), with or without a standard or high dose of ethanol, and medium-chain triglycerides (saturated fat) with a high dose of ethanol for 8 wk enterally. The dose of ethanol was increased as tolerance developed, which allowed approximately twice as much alcohol to be delivered in the high-dose group. Serum pancreatic enzymes and histology were normal after 4 wk of diets rich in unsaturated fat, with or without the standard dose of ethanol. In contrast, enzyme levels were elevated significantly by the high ethanol dose. Increases were blunted significantly by dietary saturated fat. Fibrosis and collagen alpha1(I) expression in the pancreas were not detectable after 4 wk of enteral ethanol feeding; however, they were enhanced significantly by the high dose after 8 wk. Furthermore, radical adducts detected by electron spin resonance were minimal with the standard dose; however, the high dose increased carbon-centered radical adducts as well as 4-hydroxynonenal, an index of lipid peroxidation, significantly. Radical adducts were also blunted by approximately 70% by dietary saturated fat. The animal model presented here is the first to demonstrate chronic alcohol-induced pancreatitis in a reproducible manner. The key factors responsible for pathology are the amount of ethanol administered and the type of dietary fat.

show abstract

supporting

confidence: 90%

Development of an animal model of chronic alcohol-induced pancreatitis in the rat

Kono¹,

Nakagami²,

Rusyn³

et al. 2001

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…In animal models of type 1 diabetes we and others provided evidence that the initiation of pancreatic islet inflammation critically depends on functionally active macrophages or other antigen presenting cells [23], [49]. The lack of TLR4 on innate immune cells such as dendritic cells or macrophages may limit the proinflammatory or immunostimulatory capacity of these cells rather than promote immune reactivity.…”

Section: Discussionmentioning

confidence: 97%

“…Further studies revealed that TLR4 is also able to bind endogenous structures, including heat shock protein 60 (Hsp60) [4], a dominant stress protein and a putative beta cell autoantigen assumed to be involved in the pathogenesis of type 1 diabetes [21]. In mammals, the expression of TLR4 was initially described on cells of the innate immune system, predominantly macrophages [22], which were found to contribute to the initiation and progression of beta cell-directed immune reactivity [23]. Recent investigations further proved the expression of TLR4 also by regulatory T-lymphocytes (Treg) which are characterised by the coexpression of the surface structures CD4 and CD25 [24].…”

Section: Introductionmentioning

confidence: 99%

Toll-Like Receptor 4 Deficiency Accelerates the Development of Insulin-Deficient Diabetes in Non-Obese Diabetic Mice

et al. 2013

Self Cite

View full text Add to dashboard Cite

Background/ObjectiveToll-like receptors (TLR) mediate the recognition of microbial constituents and stress-induced endogenous ligands by the immune system. They may also be involved in the maintenance or break down of tolerance against autologous antigens. The aim of our investigation was to study the consequence of TLR4 deficiency on the development of insulin-deficient diabetes in the NOD mouse.MethodsThe TLR4 defect of the C57BL/10ScN mouse was backcrossed onto the NOD background and the effect of TLR4 deficiency on diabetes development was analysed by in vivo and in vitro studies.ResultsCompared to animals with wildtype TLR4 expression (TLR4+/+), female NOD mice carrying a homozygous TLR4 defect (TLR4−/−), showed significant acceleration of diabetes development, with a younger age at diabetes onset (TLR4+/+ 177±22 d, TLR−/−: 118±21 d; p<0.01). Pancreata of 120 d old TLR4−/− NOD mice revealed increased proportions of islets with advanced stages of immune cell infiltration compared to TLR4+/+ mice (p<0.05). TLR4 deficiency did not affect the susceptibility of islet cells to the beta cell damaging mediators nitric oxide or the inflammatory cytokines tumor necrosis factor alpha, interleukin-1 beta and interferon gamma. The lack of TLR4 further had no effect on the frequency of regulatory T-cells but reduced their capacity to inhibit T-cell proliferation.ConclusionsOur findings demonstrate that TLR4 deficiency results in an acceleration of diabetes development and immune cell infiltration of islets in NOD mice. We conclude that TLR4 is involved in the progression of the insulitis process thereby controlling the development of insulin-deficient diabetes in NOD mice.

show abstract

“…The first cells to invade the islets of Langerhans are APCs such as monocytes and macrophages [1,2], followed by T-cells causing a destructive insulitis. Inflammatory mediators, such as interleukin (IL)-1β, tumour necrosis factor α (TNFα), interferon-γ and/or nitric oxide, have also been suggested to be implicated in the specific cellular destruction of β-cells in T1DM [3,4].…”

Section: Introductionmentioning

confidence: 99%

A subset of human pancreatic beta cells express functional CD14 receptors: a signaling pathway for beta cell‐related glycolipids, sulfatide and β‐galactosylceramide

Østerbye

Funda

Fundová

et al. 2010

Diabetes Metabolism Res

View full text Add to dashboard Cite

A subset of human beta-cells expresses functional CD14 receptor and thus is able to recognize both exogenous bacterial (LPS) as well as endogenous ligands (e.g. glycolipids of beta-cell origin). The CD14 expression on a subset of human beta-cells may play a role in the innate surveillance of the endocrine environment but may also contribute to innate immune mechanisms in the early stages of beta-cell aggression.

show abstract

Macrophages in Islet Destruction in Autoimmune Diabetes Mellitus

Cited by 16 publications

References 38 publications

Development of an animal model of chronic alcohol-induced pancreatitis in the rat

Development of an animal model of chronic alcohol-induced pancreatitis in the rat

Toll-Like Receptor 4 Deficiency Accelerates the Development of Insulin-Deficient Diabetes in Non-Obese Diabetic Mice

A subset of human pancreatic beta cells express functional CD14 receptors: a signaling pathway for beta cell‐related glycolipids, sulfatide and β‐galactosylceramide

Contact Info

Product

Resources

About