Alveolar macrophages in diabetes: friends or foes?

Sunahara, Karen K. S.; Martins, Joilson O.

doi:10.1189/jlb.0911488

Cited by 19 publications

(12 citation statements)

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“…Alveolar macrophages from normal hosts demonstrate an aberrant immune response that contributes to worsening infection and autoimmunity when exposed to elevated glucose concentration [ 28 ]. Insulin resistance was detected two days prior to the clinical suspicion of ventilator-associated pneumonia for critically injured patients on the glycemic control protocol [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Higher Mortality in Trauma Patients Is Associated with Stress-Induced Hyperglycemia, but Not Diabetic Hyperglycemia: A Cross-Sectional Analysis Based on a Propensity-Score Matching Approach

Rau

Chen

et al. 2017

IJERPH

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Background: Stress-induced hyperglycemia (SIH) is a form of hyperglycemia secondary to stress and commonly occurs in patients with trauma. Trauma patients with SIH have been reported to have an increased risk of mortality. However, information regarding whether these trauma patients with SIH represent a distinct group with differential outcomes when compared to those with diabetic hyperglycemia (DH) remains limited. Methods: Diabetes mellitus (DM) was determined by patient history and/or admission glycated hemoglobin (HbA1c) ≥6.5%. Non-diabetic normoglycemia (NDN) was determined by a serum glucose level <200 mg/dL in the patients without DM. Diabetic normoglycemia (DN) was determined by a serum glucose level <200 mg/dL in the patients with DM. DH and SIH was diagnosed by a serum glucose level ≥200 mg/dL in the patients with and without DM, respectively. Detailed data of these four groups of hospitalized patients, which included NDN (n = 7806), DN (n = 950), SIH (n = 493), and DH (n = 897), were retrieved from the Trauma Registry System at a level I trauma center between 1 January 2009 and 31 December 2015. Patients with incomplete registered data were excluded. Categorical data were compared with Pearson chi-square tests or two-sided Fisher exact tests. The unpaired Student’s t-test and the Mann–Whitney U-test were used to analyze normally distributed continuous data and non-normally distributed data, respectively. Propensity-score-matched cohorts in a 1:1 ratio were allocated using NCSS software with logistic regression to evaluate the effect of SIH and DH on the outcomes of patients. Results: The SIH (median [interquartile range: Q1–Q3], 13 [9–24]) demonstrated a significantly higher Injury Severity Score (ISS) than NDN (9 [4–10]), DN (9 [4–9]), and DH (9 [5–13]). SIH and DH had a 12.3-fold (95% confidence interval [CI] 9.31–16.14; p < 0.001) and 2.4-fold (95% CI 1.71–3.45; p < 0.001) higher odds of mortality, respectively, when compared to NDN. However, in the selected propensity-score-matched patient population, SIH had a 3.0-fold higher odd ratio of mortality (95% CI 1.96–4.49; p < 0.001) than NDN, but DH did not have a significantly higher mortality (odds ratio 1.2, 95% CI 0.99–1.38; p = 0.065). In addition, SIH had 2.4-fold higher odds of mortality (95% CI 1.46–4.04; p = 0.001) than DH. These results suggest that the characteristics and injury severity of the trauma patients contributed to the higher mortality of these patients with hyperglycemia upon admission, and that the pathophysiological effect of SIH was different from that of DH. Conclusions: Although there were worse mortality outcomes among trauma patients presenting with hyperglycemia, this effect was only seen in patients with SIH, but not DH when controlling for age, sex, pre-existed co-morbidities, and ISS.

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Section: Discussionmentioning

confidence: 99%

Higher Mortality in Trauma Patients Is Associated with Stress-Induced Hyperglycemia, but Not Diabetic Hyperglycemia: A Cross-Sectional Analysis Based on a Propensity-Score Matching Approach

Rau

Chen

et al. 2017

IJERPH

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“…IL-1β is a pivotal inflammatory mediator, produced by PAMPs (Pathogen-associated molecular patterns)-activated cells of innate immune system, driving the host response to control infection or lead to tissue injuries [40]. Higher mRNA expression levels of IL-1β, MCP-1, and TNF-α have been demonstrated in the alveolar macrophages (AMs) of diabetic patients that failed to control infection in contrast to normal AMs [41]. Therefore, the lasting production of IL-1β, probably released by K. pneumoniae -activated Kupffer cells or neutrophils, might contribute to the enhancement of liver injury by diabetes (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Activation of IFN-γ/STAT/IRF-1 in Hepatic Responses to Klebsiella pneumoniae Infection

et al. 2013

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Background Klebsiella pneumoniae-caused liver abscess (KLA) has become a health problem in Taiwan and is continually reported in other countries. Diabetes mellitus, the most common metabolic disorder, underlies half of the KLA patients in Taiwan. The clinical impact of KLA has been well-documented. Nevertheless, the molecular basis regarding how K. pneumoniae causes liver infection, particularly in diabetic individuals, remains unclear.Methodology/Principle FindingsAuto-bioluminescence-expressing K. pneumoniae was inoculated into diabetic mice and age-match naïve control. With the use of in vivo imaging system, translocation of the bioluminescence-expressing K. pneumoniae from intestine to extraintestinal organs, mainly the liver, was noted in 80% of the diabetic mice, whereas the same bacteria causes extraintestinal infections in only 31% of naïve mice. Besides increased morbidity, the severity of hepatic tissue injury was also enhanced in the K. pneumoniae-infected diabetic mice. Upon K. pneumoniae infection, IFN-γ production was significantly evoked in the liver. To mediate IFN-γ signal, STAT (signal transducers and activators of transcription) 1 and 3 were activated in hepatocytes, and so was the expression of IRF (interferon regulatory factor)-1. Moreover, accumulation of neutrophils which was triggered by prolonged production of IL-1β and MIP-2, and significant increases in the level of active caspase 3 and phospho-eIF2α, were exclusively revealed in the K. pneumoniae-infected diabetic mice.ConclusionThe activation of IFN-γ/STAT/IRF-1 signaling demonstrated by this work emphasizes the role of IFN-γ for mediating the hepatic response to K. pneumoniae infection.

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“…Experimental evidence suggests that the abnormally high number of inflammatory cells in adipose tissue of obese subjects and type 2 diabetes patients may promote systemic inflammation and a microenvironment favorable for neoplastic cell survival and proliferation. For instance, aberrant alveolar macrophages contribute to worsening lung infection and autoimmunity in type 2 diabetes patients (Sunahara & Martins 2012). Fritz et al (2011) have recently demonstrated that alveolar macrophages release IGF1, which stimulates neoplastic mouse lung cell proliferation through PI3K/Akt and MAPK/ERK activation.…”

Section: Insulin Resistance Immune Response Alterations and Cancer:mentioning

confidence: 99%

Insulin resistance and cancer: the role of insulin and IGFs

Djiogue¹,

Kamdje²,

Vecchio³

et al. 2012

Endocrine-Related Cancer

232

188

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Insulin, IGF1, and IGF2 are the most studied insulin-like peptides (ILPs). These are evolutionary conserved factors well known as key regulators of energy metabolism and growth, with crucial roles in insulin resistance-related metabolic disorders such as obesity, diseases like type 2 diabetes mellitus, as well as associated immune deregulations. A growing body of evidence suggests that insulin and IGF1 receptors mediate their effects on regulating cell proliferation, differentiation, apoptosis, glucose transport, and energy metabolism by signaling downstream through insulin receptor substrate molecules and thus play a pivotal role in cell fate determination. Despite the emerging evidence from epidemiological studies on the possible relationship between insulin resistance and cancer, our understanding on the cellular and molecular mechanisms that might account for this relationship remains incompletely understood. The involvement of IGFs in carcinogenesis is attributed to their role in linking high energy intake, increased cell proliferation, and suppression of apoptosis to cancer risks, which has been proposed as the key mechanism bridging insulin resistance and cancer. The present review summarizes and discusses evidence highlighting recent advances in our understanding on the role of ILPs as the link between insulin resistance and cancer and between immune deregulation and cancer in obesity, as well as those areas where there remains a paucity of data. It is anticipated that issues discussed in this paper will also recover new therapeutic targets that can assist in diagnostic screening and novel approaches to controlling tumor development.

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Alveolar macrophages in diabetes: friends or foes?

Cited by 19 publications

References 56 publications

Higher Mortality in Trauma Patients Is Associated with Stress-Induced Hyperglycemia, but Not Diabetic Hyperglycemia: A Cross-Sectional Analysis Based on a Propensity-Score Matching Approach

Higher Mortality in Trauma Patients Is Associated with Stress-Induced Hyperglycemia, but Not Diabetic Hyperglycemia: A Cross-Sectional Analysis Based on a Propensity-Score Matching Approach

Activation of IFN-γ/STAT/IRF-1 in Hepatic Responses to Klebsiella pneumoniae Infection

Insulin resistance and cancer: the role of insulin and IGFs

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