The histopathology of the pancreas in Type I (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom

Foulis, Alan K.; Liddle, C N; Farquharson, M. A.; Richmond, James; Weir, R S

doi:10.1007/bf00452061

Cited by 438 publications

(337 citation statements)

References 14 publications

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“…In our study, lymphocytic infiltration of the exocrine gland was observed in about half of the cases, but insulitis was detected in only 1 of 47 cases, which represented 25% of the cases with IDDM of recent onset. Since our study included only a small number of patients with IDDM of short duration, we could not conclude that the incidence of insulitis in Japanese patients with IDDM is lower than that in Caucasian patients with IDDM, but it was evident that lymphocytic infiltration of the exocrine gland was more common in our study than in studies of Caucasian patients reported by Foulis [7] and Gepts [3]. This discrepancy may be due to the racial difference or to differences in HLA, age or other ethnopathogenic factors.…”

Section: Discussioncontrasting

confidence: 59%

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Histopathologic Study of the Pancreas Shows a Characteristic Lymphocytic Infiltration in Japanese Patients with IDDM.

et al. 1997

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Abstract. We examined at autopsy 47 cases (22 males and 25 females) of insulin-dependent diabetes mellitus (IDDM) from 21 hospitals in Japan to clarify the pathological changes that occur in the pancreas vs. those in control patients. The mean age was 39.7 ± 13.9 (mean ± SD) years, and the duration of IDDM from clinical onset was 13.1 ± 6.5 years. Causes of death included renal complications, infections, acute diabetic complications such as ketoacidosis or hyper-or hypoglycemic coma, and atherosclerotic disease. This study revealed noticeable decreases in the islet area and beta cell area, and a slight decreases in the alpha cell area and preservation of the number of islets. Insulitis was found in only 1 case, representing 25% of the cases with a duration of IDDM of one year or less. Lymphocytic infiltration of the exocrine gland was seen in 22 cases (46.8%). Predominant phenotypes of the lymphocytes were T lymphocytes and macrophages. Fibrosis, fatty change and atrophy were also found. Although this is not a strictly age-and sex-matched study, the high incidence of lymphocytic infiltration of the exocrine pancreas indicates that the exocrine tissue as well as beta cells is the target of immune reactions in Japanese patients with IDDM.

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Section: Discussioncontrasting

confidence: 59%

“…include pen-and intra-insular inflammatory infiltrates, namely, insulitis, atrophy of islets and a decrease in or disappearance of islets and beta cells [3][4][5][6][7], but few reports have described pathological findings in Japanese IDDM patients.…”

mentioning

confidence: 99%

Histopathologic Study of the Pancreas Shows a Characteristic Lymphocytic Infiltration in Japanese Patients with IDDM.

et al. 1997

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“…vp1 immunostaining is restricted to insulin-containing islets (ICIs) In the pancreas in recent-onset type 1 diabetes, approximately 60% of the islets are insulin deficient and the remainder contain residual insulin-secreting beta cells [18]. An analysis was made of the distribution of vp1-positive cells between insulin-deficient islets (IDIs) and ICIs in serial sections from ten patients with frequent vp1-positive endocrine cells.…”

Section: Resultsmentioning

confidence: 99%

“…Individuals Formalin-fixed, paraffin-embedded pancreatic autopsy tissue from 72 patients with recent-onset type 1 diabetes mellitus, whose pancreatic histology has been described previously [18] was used, with ethical permission. The cases were from various hospitals and had been fixed in buffered formalin, formol saline, formol saline with added mercuric chloride, or Bouin's fixative, with no standardisation of fixation time.…”

Section: Methodsmentioning

confidence: 99%

The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes

et al. 2009

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Aims/hypothesis Evidence that the beta cells of human patients with type 1 diabetes can be infected with enterovirus is accumulating, but it remains unclear whether such infections occur at high frequency and are important in the disease process. We have now assessed the prevalence of enteroviral capsid protein vp1 (vp1) staining in a large cohort of autopsy pancreases of recent-onset type 1 diabetic patients and a range of controls. Methods Serial sections of paraffin-embedded pancreatic autopsy samples from 72 recent-onset type 1 diabetes patients and up to 161 controls were immunostained for insulin, glucagon, vp1, double-stranded RNA activated protein kinase R (PKR) and MHC class I. Results vp1-immunopositive cells were detected in multiple islets of 44 out of 72 young recent-onset type 1 diabetic patients, compared with a total of only three islets in three out of 50 neonatal and paediatric normal controls. vp1 staining was restricted to insulin-containing beta cells. Among the control pancreases, vp1 immunopositivity was also observed in some islets from ten out of 25 type 2 diabetic patients. A strong correlation was established between islet cell vp1 positivity and PKR production in insulin-containing islets of both type 1 and type 2 diabetic patients, consistent with a persistent viral infection of the islets. Conclusions/interpretation Immunoreactive vp1 is commonly found in the islets of recent-onset type 1 diabetes patients, but only rarely in normal paediatric controls. vp1 immunostaining was also observed in some islets of type 2 diabetes patients, suggesting that the phenomenon is not restricted to type 1 diabetes patients.

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“…Consequently, zinc and iron are not easily discriminated and some iron ends up together with zinc in the insulin-storing granules, which may explain why in hemachromatosis and other iron-overload conditions, diabetes is a common complication (bronze-diabetes). It can be assumed that in -cells an iron-enriched lysosomal compartment might undergo LMP and associated apoptosis even if only normal concentrations of cytosolic hydrogen peroxide are present (Olejnicka et al, 1999 -cells (Augstein et al, 1998, Eisenbarth, 1986, Foulis et al, 1986, O'Brien et al, 1997. Since invading macrophages and neutrophils produce ROS, the extracellular environment of the -cells in this autoimmune disease might be highly oxidative.…”

Section: Lysosomal Iron and Diabetesmentioning

confidence: 99%

The role of lysosomes in iron metabolism and recycling

Kurz

Eaton

Brunk

2011

The International Journal of Biochemistry & Cell Biology

167

134

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Iron is the most abundant transition metal in the earths crust. It cycles easily between ferric (oxidized; Fe(III)) and ferrous (reduced; Fe(II)) and readily forms complexes with oxygen, making this metal a central player in respiration and related redox processes. However, loose iron, not within heme or iron-sulfur cluster proteins, can be destructively redox-active, causing damage to almost all cellular components, killing both cells and organisms. This may explain why iron is so carefully handled by aerobic organisms. Iron uptake from the environment is carefully limited and carried out by specialized iron transport mechanisms. One reason that iron uptake is tightly controlled is that most organisms and cells cannot efficiently excrete excess iron. When even small amounts of intracellular free iron occur, most of it is safely stored in a non-redox-active form in ferritins. Within nucleated cells, iron is constantly being recycled from aged iron-rich organelles such as mitochondria and used for construction of new organelles. Much of this recycling occurs within the lysosome, an acidic digestive organelle. Because of this, most lysosomes contain relatively large amounts of redox-active iron and are therefore unusually susceptible to oxidant-mediated destabilization or rupture. In many cell types, iron transit through the lysosomal compartment can be remarkably brisk. However, conditions adversely affecting lysosomal iron handling (or oxidant stress) can contribute to a variety of acute and chronic diseases. These considerations make normal and abnormal lysosomal handling of iron central to the understanding and, perhaps, therapy of a wide range of diseases

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The histopathology of the pancreas in Type I (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom

Cited by 438 publications

References 14 publications

Histopathologic Study of the Pancreas Shows a Characteristic Lymphocytic Infiltration in Japanese Patients with IDDM.

Histopathologic Study of the Pancreas Shows a Characteristic Lymphocytic Infiltration in Japanese Patients with IDDM.

The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes

The role of lysosomes in iron metabolism and recycling

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