Downregulation of interleukin-10 receptor (IL-10R) along with low serum IL-10 levels in newly diagnosed type 2 diabetes mellitus patients

Abhilasha,; Mitra, Prasenjit; Suri, Shoba; Saxena, Indu; Shukla, Ravindra; Shukla, Kamla Kant; Sharma, Praveen

doi:10.1016/j.genrep.2021.101251

Cited by 8 publications

(9 citation statements)

References 21 publications

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“…found increased levels with reduced function of IL-10 in T2DM patients ( 29 ), our results are in agreement with Abhilasha et al. ( 55 ), where lower levels of IL-10 were found. While this finding was not significant, our study revealed lower levels of IL-10 in prediabetes compared to controls, in contrast to results obtained by Wang et al.…”

Section: Discussionsupporting

confidence: 93%

Inflammation, oxidative stress and mitochondrial dysfunction in the progression of type II diabetes mellitus with coexisting hypertension

et al. 2023

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IntroductionType II diabetes mellitus (T2DM) is a metabolic disorder that poses a serious health concern worldwide due to its rising prevalence. Hypertension (HT) is a frequent comorbidity of T2DM, with the co-occurrence of both conditions increasing the risk of diabetes-associated complications. Inflammation and oxidative stress (OS) have been identified as leading factors in the development and progression of both T2DM and HT. However, OS and inflammation processes associated with these two comorbidities are not fully understood. This study aimed to explore changes in the levels of plasma and urinary inflammatory and OS biomarkers, along with mitochondrial OS biomarkers connected to mitochondrial dysfunction (MitD). These markers may provide a more comprehensive perspective associated with disease progression from no diabetes, and prediabetes, to T2DM coexisting with HT in a cohort of patients attending a diabetes health clinic in Australia.MethodsThree-hundred and eighty-four participants were divided into four groups according to disease status: 210 healthy controls, 55 prediabetic patients, 32 T2DM, and 87 patients with T2DM and HT (T2DM+HT). Kruskal-Wallis and χ2 tests were conducted between the four groups to detect significant differences for numerical and categorical variables, respectively.Results and discussionFor the transition from prediabetes to T2DM, interleukin-10 (IL-10), C-reactive protein (CRP), 8-hydroxy-2’-deoxyguanosine (8-OHdG), humanin (HN), and p66Shc were the most discriminatory biomarkers, generally displaying elevated levels of inflammation and OS in T2DM, in addition to disrupted mitochondrial function as revealed by p66Shc and HN. Disease progression from T2DM to T2DM+HT indicated lower levels of inflammation and OS as revealed through IL-10, interleukin-6 (IL-6), interleukin-1β (IL-1β), 8-OHdG and oxidized glutathione (GSSG) levels, most likely due to antihypertensive medication use in the T2DM +HT patient group. The results also indicated better mitochondrial function in this group as shown through higher HN and lower p66Shc levels, which can also be attributed to medication use. However, monocyte chemoattractant protein-1 (MCP-1) levels appeared to be independent of medication, providing an effective biomarker even in the presence of medication use. The results of this study suggest that a more comprehensive review of inflammation and OS biomarkers is more effective in discriminating between the stages of T2DM progression in the presence or absence of HT. Our results further indicate the usefulness of medication use, especially with respect to the known involvement of inflammation and OS in disease progression, highlighting specific biomarkers during disease progression and therefore allowing a more targeted individualized treatment plan.

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Section: Discussionsupporting

confidence: 93%

Inflammation, oxidative stress and mitochondrial dysfunction in the progression of type II diabetes mellitus with coexisting hypertension

et al. 2023

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“…The LMCs cytokine protein expression in response to LPS showed an up-regulation of IL-6, IL-1A and IL-1B as previously reported [39] and an upregulation of IL-7 and IL-33 and a down-regulation of IL-10 and IL-15. The response of the LMCs to LPS showed a typical trend towards in ammation with the up-regulation of IL-6, IL-1A, and IL-1B and a downregulation of IL-10 in both mRNA and protein expression [40], [41]. IL-33, an alarmin cytokine, has been implicated in having roles in chronic in ammatory conditions and may have a role in signalling cellular damage and in ammatory disease pathogenesis [42].…”

Section: Discussionmentioning

confidence: 99%

Amyloid Beta – induced leptomeningeal cell JAK/STAT signalling regulates inflammatory responses of astrocytes in Alzheimer’s Disease

Abubaker,

Stanton,

Mahon

et al. 2024

Preprint

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The pathological signature of Alzheimer's disease (AD) includes the accumulation of toxic protein aggregates, mainly consisting of amyloid beta (Aβ). Recent strides in fundamental research underscore the pivotal role of waste clearance mechanisms in the brain suggesting it may be an early indication of early-onset AD. This study delves into the involvement of leptomeningeal cells (LMCs), crucial components forming integral barriers within the clearance system, in the context of AD. In this study, we examined the inflammatory responses of LMCs to Aβ, investigating their morphological changes and oxidative responses. The LMCs showed no changes in growth, viability, oxidative stress and vimentin expression in the presence of Aβ. Furthermore, LMCs exhibited a proinflammatory response unique to the Aβ when compared to an LPS control. When treated with JAK/STAT inhibitors, LMCs' inflammatory responses reverted to control levels, suggesting a crucial role of the JAK/STAT pathway in mediating LMC responses to Aβ-induced inflammation. Lastly, Aβ treated LMCs conditioned media demonstrated a reduction in S100B levels in astrocytes compared to both astrocyte control and Aβ-treated astrocytes. This observation suggests a potential anti-inflammatory role of LMCs toward astrocytes, potentially impacting the intricate cellular interplay in AD.

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“…Interleukin-10 (IL-10) is an immune cell-produced anti-inflammatory cytokine distinguished by its capacity to prevent macrophage activation 57 . Inflammation is caused by IL-10 or IL-10 Receptor (IL-10R) signaling defects, which may be a valid link in the development of T2DM 58 . In people with T2DM, interleukin-1beta (IL-1β) is a significant inflammatory agent 59 .…”

Section: Mitochondrial Peptide Markers For Diabetes Progression and C...mentioning

confidence: 99%

Comparative Analysis of Biomarkers in Type 2 Diabetes Patients with and without Comorbidities: Insights into the Role of Hypertension and Cardiovascular Disease

Savvopoulos,

Hatzikirou,

Jelinek

2024

Preprint

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Background: Type 2 diabetes mellitus (T2DM) are 90% of diabetes cases, and its prevalence and incidence, including comorbidities, are rising worldwide. Clinically, diabetes and associated comorbidities are identified by biochemical and physical characteristics including glycaemia, glycated hemoglobin (HbA1c), and tests for cardiovascular, eye and kidney disease. Objectives: Diabetes may have a common etiology based on inflammation and oxidative stress that may provide additional information about disease progression and treatment options. Thus, identifying high-risk individuals can delay or prevent diabetes and its complications. Design: In patients with or without hypertension and cardiovascular disease, as part of progression from no diabetes to T2DM, this research studied the changes in biomarkers between control and prediabetes, prediabetes to T2DM, and control to T2DM, and classified patients based on first-attendance data. Control patients and patients with hypertension, cardiovascular, and with both hypertension and cardiovascular diseases are 156, 148, 61, and 216, respectively. Methods: Linear discriminant analysis is used for classification method and feature importance, This study examined the relationship between Humanin and mitochondrial protein (MOTSc), mitochondrial peptides associated with oxidative stress, diabetes progression, and associated complications. Results: MOTSc, reduced glutathione and glutathione disulfide ratio (GSH/GSSG), interleukin-1beta (IL-1beta), and 8-isoprostane were significant (p<0.05) for the transition from prediabetes to T2DM, highlighting the importance of mitochondrial involvement. Complement component 5a (C5a) is a biomarker associated with disease progression and comorbidities, with GSH/GSSG, monocyte chemoattractant protein-1 (MCP-1), and 8-isoprostane being the most important biomarkers. Conclusions: Comorbidities affect the hypothesized biomarkers as diabetes progresses. Mitochondrial oxidative stress indicators, coagulation, and inflammatory markers help assess diabetes disease development and provide appropriate medications. Future studies will examine longitudinal biomarker evolution.

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Downregulation of interleukin-10 receptor (IL-10R) along with low serum IL-10 levels in newly diagnosed type 2 diabetes mellitus patients

Cited by 8 publications

References 21 publications

Inflammation, oxidative stress and mitochondrial dysfunction in the progression of type II diabetes mellitus with coexisting hypertension

Inflammation, oxidative stress and mitochondrial dysfunction in the progression of type II diabetes mellitus with coexisting hypertension

Amyloid Beta – induced leptomeningeal cell JAK/STAT signalling regulates inflammatory responses of astrocytes in Alzheimer’s Disease

Comparative Analysis of Biomarkers in Type 2 Diabetes Patients with and without Comorbidities: Insights into the Role of Hypertension and Cardiovascular Disease

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