The endocrine pancreas of spontaneously diabetic mice: microangiopathy as revealed by transmission electron microscopy

Nakamura, Mitsuo; Kitamura, Hirokazu; Konishi, Sadanori; Nishimura, Masahiko; Ono, Junko; Ina, Keisuke; Shimada, Toshio; Takaki, Ryosaburo

doi:10.1016/0168-8227(95)01155-2

Cited by 42 publications

(41 citation statements)

References 41 publications

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“…In db/db mice, there is capillary and pericyte hypertrophy (41). The apparent hypertrophy of endothelial cells is evident in both light microscopy and TEM of endothelial cells described in the present study.…”

Section: Discussionsupporting

confidence: 49%

Islet Microvasculature in Islet Hyperplasia and Failure in a Model of Type 2 Diabetes

et al. 2006

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Gene expression profiling of islets from pre-diabetic male Zucker diabetic fatty (ZDF) rats showed increased expression of hypoxia-related genes, prompting investigation of the vascular integrity of the islets. The islet microvasculature was increased approximately twofold in young male ZDF rats by both morphometric analysis and quantifying mRNA levels of endothelial markers. ZDF rats at 12 weeks of age showed a significant reduction in the number of endothelial cells, which was prevented by pretreatment with pioglitazone. Light and electron microscopy of normoglycemic 7-week-old ZDF rats showed thickened endothelial cells with loss of endothelial fenestrations. By 12 weeks of age, there was disruption of the endothelium and intra-islet hemorrhage. Islets from 7-and 12-week-old ZDF rats showed an approximate three-and twofold increase in vascular endothelial growth factor (VEGF)-A mRNA and VEGF protein secretion, respectively, compared with lean controls. Thrombospondin-1 mRNA increased in 7-and 12-week-old rats by 2-and 10-fold, respectively, and was reduced by 50% in 12-week-old rats pretreated with pioglitazone. Islets from young male control rats induced migration of endothelial cells in a collagen matrix only after pretreatment with matrix metalloproteinase (MMP)-9. Islets from 7-week-old ZDF rats showed a fivefold increase in migration score compared with wild-type controls, even without MMP-9 treatment. Islets from 15-week-old ZDF rats did not induce migration; rather, they caused a significant rounding up of the duct-derived cells, suggesting a toxic effect. These data suggest that in the ZDF rat model of type 2 diabetes, an inability of the islet to maintain vascular integrity may contribute to ␤-cell failure.

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Section: Discussionsupporting

confidence: 49%

Islet Microvasculature in Islet Hyperplasia and Failure in a Model of Type 2 Diabetes

et al. 2006

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“…In rodent models of type 2 diabetes, a large increase in islet volume/mass is commonly observed, largely as a result of increased beta cell proliferation and vascular density [108][109][110][111][112][113]. This massive increase in beta cell mass is attributed to an intra-islet, rather than systemic, insulin resistance [84,114].…”

Section: Islet Structure-function and Diabetesmentioning

confidence: 99%

New insights into the architecture of the islet of Langerhans: a focused cross-species assessment

et al. 2015

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The human genome project and its search for factors underlying human diseases has fostered a major human research effort. Therefore, unsurprisingly, in recent years we have observed an increasing number of studies on human islet cells, including disease approaches focusing on type 1 and type 2 diabetes. Yet, the field of islet and diabetes research relies on the legacy of rodent-based investigations, which have proven difficult to translate to humans, particularly in type 1 diabetes. Whole islet physiology and pathology may differ between rodents and humans, and thus a comprehensive cross-species as well as species-specific view on islet research is much needed. In this review we summarise the current knowledge of interspecies islet cytoarchitecture, and discuss its potential impact on islet function and future perspectives in islet pathophysiology research.

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“…In rodent models of obesity and hypertension, histological changes in islet pericytes, including hypertrophy and an increase in staining density of the surface marker neuronglial antigen 2 (NG2), have been observed [4,5,18,19], suggesting pericytes' morphological plasticity in response to the disturbances of the circulation. In the progression of type 1 diabetes, although the role of pericytes is not understood, vascular swelling and leakage have been imaged in insulitis and used as an indicator of islet inflammation in NOD mice [20,21].…”

Section: Introductionmentioning

confidence: 99%

Plasticity of Schwann cells and pericytes in response to islet injury in mice

et al. 2013

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Aims/hypothesis Islet Schwann (glial) cells and pericytes are the microorgan's accessory cells positioned at the external and internal boundaries facing the exocrine pancreas and endothelium, respectively, adjacent to the endocrine cells. Plasticity of glial cells and pericytes is shown in the glial scar formation after injury to the central nervous system. It remains unclear whether similar reactive cellular responses occur in insulitis. We applied three-dimensional (3D) histology to perform qualitative and quantitative analyses of the islet Schwann cell network and pericytes in normal, streptozotocin-injected (positive control of gliosis) and NOD mouse models. Methods Vessel painting paired with immunostaining of mouse pancreatic tissue was used to reveal the islet Schwann cells and pericytes and their association with vasculature. Transparent islet specimens were prepared by optical clearing to facilitate 3D confocal microscopy for panoramic visualisation of the tissue networks.Results In-depth microscopy showed that the islet Schwann cell network extends from the peri-islet domain into the core. One week after streptozotocin injection, we observed intraislet perivascular gliosis and an increase in pericyte density. In early/moderate insulitis in the NOD mice, perilesional gliosis occurred at the front of the lymphocytic infiltration with atypical islet Schwann cell morphologies, including excessive branching and perivascular gliosis. Meanwhile, pericytes aggregated on the walls of the feeding arteriole at the peri-and intralesional domains with a marked increase in surface marker density. Conclusions/interpretationThe reactive cellular responses demonstrate plasticity and suggest a stop-gap mechanism consisting of the Schwann cells and pericytes in association with the islet lesion and vasculature when injury occurs.

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The endocrine pancreas of spontaneously diabetic mice: microangiopathy as revealed by transmission electron microscopy

Cited by 42 publications

References 41 publications

Islet Microvasculature in Islet Hyperplasia and Failure in a Model of Type 2 Diabetes

Islet Microvasculature in Islet Hyperplasia and Failure in a Model of Type 2 Diabetes

New insights into the architecture of the islet of Langerhans: a focused cross-species assessment

Plasticity of Schwann cells and pericytes in response to islet injury in mice

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