Lazaroid antioxidant reduces incidence of diabetes and insulitis in nonobese diabetic mice.
21
Citation
0
Reference
10
Related Paper
Citation Trend
Keywords:
Insulitis
NOD mice
Pancreatic Islets
Cite
BETA (programming language)
NOD mice
Cite
Citations (11)
Autoimmune diabetes in the popular nonobese diabetic (NOD) mouse results from a T-cell–mediated destruction of the insulin-producing β-cells (1) and serves as a model for human type 1 diabetes (2,3). The mechanisms that initiate early peri-islet inflammation and the destructive components that arise later specifically targeting β-cells occur naturally in NOD mice (2,3). Two obstacles hinder our progress in unraveling the rudiments of type 1 diabetes: 1 ) the identification of the antigens involved in the earliest stages of autoimmunity and 2 ) the event(s) that provokes the initial autoimmunity and loss of homeostasis in the islets. The hope has been that the former would aid in sorting out the latter.
The NOD mouse provides us with a framework for understanding T-cell–mediated autoimmune diseases in general. Discovering the nature of the initial organ-infiltrating cells is a key to the prevention of inflammatory autoimmune disease. Does spontaneous insulitis, which precedes type 1 diabetes, begin by a random accumulation of lymphocytes into the pancreatic islets, or is there an essential temporal pattern to the activation and recruitment of organ-specific lymphocytes? An answer to this question seems essential to our grasping the complexities of disease susceptibility and onset. Infectious agents have long been postulated to have a role as incendiary triggers for abnormal tissue inflammation and the genesis of a tissue-specific adaptive autoimmune/immune response. Either through …
Insulitis
NOD mice
Pancreatic Islets
Cite
Citations (1)
Insulitis
NOD mice
Pancreatic Islets
Cite
Citations (21)
Pancreatic Islets
BETA (programming language)
Human physiology
Cite
Citations (20)
Type 1 diabetes (T1D) is an autoimmune disease in which immune cells target the pancreatic islets and destroy the β-cells, resulting in hyperglycemia and decreased plasmatic insulin levels. The non-obese diabetic (NOD) mouse is the most used animal model for studying diabetes because it spontaneously develops T1D and shares similarities with the human disease. A hallmark feature of this model is the appearance of insulitis, defined as an inflammatory cell infiltration of the pancreatic islets. However, a small percentage of NOD mice do not develop overt diabetes even after 28-35 weeks of age. Thus, we questioned the status of the pancreatic islets in these non-diabetic NOD mice, with particular focus on islet inflammation and plasmatic insulin levels, in comparison to pre-diabetic (11 weeks old) and new-onset diabetic mice. Diabetes progression was evaluated by assessing blood glucose and pancreas histology. The inflammatory score was determined on Hematoxylin-Eosin (HE)-stained sections of pancreas. Plasma insulin was detected by enzyme-linked immunosorbent assay (ELISA). The results showed that inflammation increased in an age-dependent manner in all mice, irrespective of their diabetic status. Mostly affected within the analyzed groups were the 28 weeks old non-diabetic NOD mice, in which insulin production was reduced and inversely correlated with the inflammatory status. We conclude that in NOD mice, pancreatic inflammation progresses independently of diabetes onset and clinical signs of disease. Most likely, the NOD females that do not develop overt diabetes preserve a small mass of functional β-cells, which is able to provide the physiological insulin levels and avoid diabetes onset.
Insulitis
NOD mice
Pancreatic Islets
Cite
Citations (5)
textabstractType 1 diabetes is a disease that results from a disturbed glucose metabolism
due to a deficiency in insulin production. This deficiency is the consequence of immune-
mediated damage to the insulin-producing s-cells. The cause of type 1 diabetes is
presently unknown and probably multifactorial. The initiation and progression of the
inflammatory process that destroys the s-cells involves the interplay of environmental
factors with an autoimmune-prone genetic background. Abnormal immune regulation
explains the autoimmune phenomena observed in diabetic patients and in spontaneous
animal models for the disease to a limited extent only. The precise reason for the
immune system to target the pancreatic islets of Langerhans is still unclear.
The pathogenic process in the pancreas is characterized by the pathology-
related intra-islet infiltration of T and B-lymphocytes that mediate islet destruction. This T
and B-cell infiltration is preceded by an accumulation of macrophages and dendritic cells
at the islet periphery. The early peri-islet accumulation of these antigen presenting cells
probably reflects the first response of the immune system that is progressively heading
for islet destruction.
Macrophages are involved in every step of the diabetogenic process. In the non-
obese diabetic (NOD) mouse that spontaneously develops diabetes, various
macrophage-abnormalities like defective maturation, reduced phagocytosis and
increased production of IL-12, have been described previously. Moreover, macrophages
are present in higher numbers in the pancreas of the NOD mouse from birth onwards,
randomly distributed in the connective tissue and exocrine parenchyma.
In this thesis we present the results of our studies on the murine pancreatic
macrophage compartment. We have questioned in particular the possible underlying
causes for the abnormal early peri-islet accumulation of macrophages. Therefore, the
studies were performed with an emphasis on the interactions of macrophages with the
extracellular matrix of the pancreatic connective tissue.
Insulitis
NOD mice
Pancreatic Islets
Cite
Citations (0)
NOD mice
Insulitis
Human physiology
Cite
Citations (24)
Insulitis
Probucol
NOD mice
Deflazacort
Pancreatic Islets
Cite
Citations (28)
Abstract: In type 1 diabetes, environmentally induced early‐limited beta cell damage may pre‐empt the subsequent immune‐mediated beta cell destruction. Low doses of streptozotocin (Stz), given early to diabetes‐prone mice, may cause limited beta cell destruction during the early phase and precipitate diabetes. Here, we aimed to see if young NOD mice are more diabetes‐sensitive to various multiple low doses of Stz than nondiabetes‐prone mice. We also determined the molecular pathology of islets following administration of the diabetogen. Female NOD and CD‐1 mice received 5 daily doses of Stz at day 21 (20, 30, and 40 mg/kg body weight; 18 mice per group) or diluent, and diabetes was monitored. Pancreas were studied histochemically and immunohistochemically at various time points after Stz administration. Following administration of Stz, NOD mice showed a much earlier onset and increased diabetes rate, at all three doses, than CD‐1 mice. By day 80, the final diabetes rates following the 40, 30, and 20 mg dose in NOD mice were 95%, 85%, and 33%, respectively, compared with 33%, 28%, and 5.5%, respectively, in CD‐1 mice. However, following the 20 mg dose, only 2 of the 12 remaining NOD mice developed the disease between 90 and 250 days compared with 19 of 24 NOD mice that did not receive Stz at day 21. Stz‐administered NOD and CD‐1 mice showed an initial loss of beta cells, with redistribution of islet endocrine cells, early macrophage infiltration, and increasing insulitis.
Insulitis
NOD mice
Cite
Citations (7)