The allergic inflammatory reaction in neonatal streptozotocininduced diabetic rats: evidence of insulin resistance and microvascular dysfunction

Cavalher-Machado, Simone C.; Cuman, Roberto Kenji Nakamura; Sartoretto, Juliano L.; Martins, Joilson O.; Lima, Wothan Tavares de; Martins, Marco A.; Silva, P. M. R.; Sannomiya, Paulina

doi:10.1007/s00011-008-8047-0

Cited by 8 publications

(4 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data support and extend our prior findings [ 6 ] and resonate with prior findings showing that at an epidemiological level, Type I diabetes incidence is negatively correlated with atopy, and that surgically or chemically pancreatectomized animals are broadly protected from anaphylaxis and refractory to anaphylatoxins. All of these studies suggest some linkage between mast-cell mediated responses and the set point of insulin the body [ 9 , 10 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mast cells and basophils bear the insulin receptor, and are regulated by insulin levels. Examples of this regulation include direct evidence for insulin promotion of proliferation in immature bone marrow derived mast cells (BMMC) [ 8 ], and at the whole organism level a linkage between insulin and mast cell pro-inflammatory potential is indicated by a number of studies showing that chemically or surgically-pancreatectomized mice are defective in anaphylactic responses despite basically normal mast cell numbers [ 9 , 10 ]. Mast cells appear to contribute to outcomes in aspects of the metabolic syndrome, [ 11 , 12 ] especially in adipose depots [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transcriptional and Functional Plasticity Induced by Chronic Insulin Exposure in a Mast Cell-Like Basophilic Leukemia Cell Model

et al. 2017

View full text Add to dashboard Cite

ObjectiveSecretory granules (SG) and lipid bodies (LB) are the primary organelles that mediate functional responses in mast cells. SG contains histamine and matrix-active proteases, while LB are reservoirs of arachidonic acid and its metabolites, precursors for rapid synthesis of eicosanoids such as LTC4. Both of these compartments can be dynamically or ontologically regulated, with metabolic and immunological stimuli altering lipid body content and granule numbers responding to contextual signals from tissue. We previously described that chronic in vitro or in vivo hyperinsulinemia expands the LB compartment with a concomitant loss of SG capacity, suggesting that this ratio is dynamically regulated. The objective of the current study is to determine if chronic insulin exposure initiates a transcriptional program that biases model mast cells towards a lipogenic state with accompanying loss of secretory granule biogenesis.MethodsWe used a basophilic leukemic cell line with mucosal mast cell-like features as a model system. We tested the hypothesis that chronic insulin exposure initiates a transcriptional program that biases these model mast cells towards a lipogenic state with accompanying loss of secretory granule biogenesis. Transcriptional arrays were used to map gene expression patterns. Biochemical, immunocytochemical and mediator release assays were used to evaluate organelle numbers and functional responses.ResultsIn a mucosal mast cell model, the rat basophilic leukemia line RBL2H3, mast cell granularity and SG numbers are inversely correlated with LB numbers. Chronic insulin exposure appears to modulate gene networks involved in both lipid body biogenesis and secretory granule formation. Western blot analysis confirms upregulation of protein levels for LB proteins, and decreases in proteins that are markers for SG cargo.ConclusionsThe levels of insulin in the extracellular milieu may modify the phenotype of mast cell-like cells in vitro.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcriptional and Functional Plasticity Induced by Chronic Insulin Exposure in a Mast Cell-Like Basophilic Leukemia Cell Model

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Among different clinical conditions, acute lung injury is a response to the damage of lung or an additional reaction to a systemic inflammatory response which leads to sepsis. In various clinical studies, it was observed that the occurrence of sepsis grows in the patients suffering from diabetes [ 2 ]. There are clinical evidences that the cases and intensity of acute lung injury instigated by direct conditions are less in diabetics.…”

Section: Introductionmentioning

confidence: 99%

Correlation of Impaired NF-kB Activation in Sepsis-Induced Acute Lung Injury (ALI) in Diabetic Rats

Chen

Sun

Zhang

et al. 2021

Journal of Healthcare Engineering

View full text Add to dashboard Cite

Background. The allergic lung inflammation is reduced in the diabetic rats which can be restored by treating it with insulin. As observed in multiple studies, the diabetic patients are more vulnerable to infections and their inflammatory reactions. There are confirmations on insulin and its effects control the inflammatory reactions. Objective. This study was performed to understand the correlation of impaired NF-kB activation in sepsis-induced acute lung injury (ALI) in diabetic rats. Material and Methods. Streptozotocin was used for induction of diabetes and sepsis was induced by colon ligation puncture surgery. Post 6 hours of CLP, the lungs in the groups were analyzed for cell infiltration using broncho-alveolar lavage. The lungs were removed for histopathological analysis at the end of study where the bronchioles, alveoli, and edema were analyzed and compared. Cell expressions quantified by the help of antibodies and inflammatory events were analyzed. Results. Diabetic rats developed mild acute lung injury due to the suppression of activation of NF-kB in alveolar macrophages. Conclusion. Even the diabetic rats were more susceptible to sepsis in comparison to the nondiabetic rats, but the NF-kB suppression has a major role to play in the faint symptoms of ALI.

show abstract

“…Hyperglycemia and insulin resistance are common in severe illness and are associated with adverse outcomes [52][53][54]. It has been discussed that in critically ill patients a single drug is unlikely to be of significant benefit.…”

Section: Protective Effect Of Insulinmentioning

confidence: 99%

Briefs on Insulin and Innate Immune Response

Sunahara

Sannomiya

Martins

2012

Cell Physiol Biochem

View full text Add to dashboard Cite

Insulin is a pivotal regulator of glucose metabolism and exerts an important anabolic function throughout the body. Insulin commands the glucose uptake by the cells and might control the processes in which there is need for energy such as mitogenesis and gene transcription. In certain conditions, diabetes mellitus for example, when insulin is diminished, the homeostasis of many tissues and organs are broken what can lead to a higher mortality due to an enhanced susceptibility to infections. This vulnerability to infections can partially be explained by a change in response to inflammation. In fact, diabetic animals and patients show a deficient inflammatory response. Many animal models have shown that neutrophils chemotaxis and recruitment are dampened and macrophages from diabetic patients have low phagocytic and microbicidal activities. In most cases, once insulin therapy is introduced, clinical symptoms and signs can be reverted. In addition, there are a number of studies trying to demystify pathways under insulin command. Researchers are also trying to understand how insulin is able to keep inflammatory response under control, restores innate immune cells ability to fight against pathogens and harmlessly activates adaptive immunity response. This review provides an overview on how inflammatory response is driven in the absence of insulin in diabetes and discusses recent findings on the influence of insulin on innate imune response. At the end, some signaling pathways are also highlighted and important enzymes and proteins that control DNA transcription are presented.

show abstract

The allergic inflammatory reaction in neonatal streptozotocininduced diabetic rats: evidence of insulin resistance and microvascular dysfunction

Abstract: Data suggest that the reduction of allergic inflammatory reactions in nSTZ rats is restricted to microvascular dysfunctions and associated, probably, with insulin resistance in lung microvascular endothelium.

Cited by 8 publications

References 40 publications

Transcriptional and Functional Plasticity Induced by Chronic Insulin Exposure in a Mast Cell-Like Basophilic Leukemia Cell Model

Transcriptional and Functional Plasticity Induced by Chronic Insulin Exposure in a Mast Cell-Like Basophilic Leukemia Cell Model

Correlation of Impaired NF-kB Activation in Sepsis-Induced Acute Lung Injury (ALI) in Diabetic Rats

Briefs on Insulin and Innate Immune Response

Contact Info

Product

Resources

About