Cyclooxygenase 2, toll-like receptor 4 and interleukin 1β mRNA expression in atherosclerotic plaques of type 2 diabetic patients

The regulation by insulin of the expression of the p85α regulatory subunit of phosphoinositide 3-kinase (PI 3-kinase) is impaired in skeletal muscle and adipose tissue of type 2 diabetic patients. The gene encoding p85α (named grb-1) can generate several variants by alternative splicing, all being able to activate the p110 catalytic subunits of PI 3-kinase. Our aims were (i) to determine the mRNA expression profiles of these variants in human skeletal muscle and adipose tissue; (ii) to investigate the effect of insulin on their expression in vivo and in vitro in muscle and (iii) to verify whether this regulation is defective in type 2 diabetes. We determined the human genomic organization of grb-1 and set up reverse transcriptase competitive PCR assays for the quantification of each mRNA variant. In muscle, p85α and p50α mRNAs were the most abundant, and p55α represented less than 20% of all grb-1-derived mRNAs. In adipose tissue, p85α was expressed predominantly and p55α mRNA was not detectable. These expression profiles were not different in type 2 diabetics. During a 3h hyperinsulinaemic clamp, insulin increased the mRNA expression of the three variants in muscle of control subjects. In diabetic patients, the effect of insulin on p85α and p50α mRNAs was blunted, and largely reduced on p55α transcripts. In cultured human myotubes, up-regulation of p85α, p55α and p50α mRNAs by insulin was abolished by LY294002 (10μM) and by rapamycin (50nM), suggesting that the PI 3-kinase/protein kinase B/p70 S6 kinase pathway could be involved in the stimulation of grb-1 gene expression by insulin in human muscle cells.

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Hydrogen gas production is associated with reduced interleukin-1β mRNA in peripheral blood after a single dose of acarbose in Japanese type 2 diabetic patients

European Journal of Pharmacology ◽

10.1016/j.ejphar.2015.04.051 ◽

2015 ◽

Vol 762 ◽

pp. 96-101 ◽

Cited By ~ 3

Author(s):

Atsuko Tamasawa ◽

Kazuki Mochizuki ◽

Natsuyo Hariya ◽

Miyoko Saito ◽

Hidenori Ishida ◽

...

Keyword(s):

Single Dose ◽

Peripheral Blood ◽

Gas Production ◽

Hydrogen Gas ◽

Interleukin 1Β ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Type 2 Diabetic

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Patterns of Toll-Like Receptor Expressions and Inflammatory Cytokine Levels and Their Implications in the Progress of Insulin Resistance and Diabetic Nephropathy in Type 2 Diabetic Patients

Frontiers in Physiology ◽

10.3389/fphys.2020.609223 ◽

2020 ◽

Vol 11 ◽

Author(s):

Rofyda H. Aly ◽

Amr E. Ahmed ◽

Walaa G. Hozayen ◽

Alaa Mohamed Rabea ◽

Tarek M. Ali ◽

...

Keyword(s):

Insulin Resistance ◽

Renal Failure ◽

Proinflammatory Cytokines ◽

Normal Subjects ◽

Diabetic Patients ◽

Toll Like Receptor ◽

Type 2 Diabetic Patients ◽

Tlr4 Mrna ◽

Type 2 Diabetic

Background: Diabetic nephropathy (DNP) is a type 2 diabetes mellitus (T2DM) chronic complication, which is the largest single cause of end-stage kidney disease. There is an increasing evidence of the role of inflammation and Toll-like receptors (TLRs) as part of innate immune system in its development and progression. In addition, Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) downward signaling causes the production of proinflammatory cytokines, which can induce insulin (INS) resistance in T2DM.Objective: The goal of this study was to estimate the expression of TLRs (TLR2 and TLR4) in relation to inflammation and INS resistance in nephrotic type 2 diabetic patients with or without renal failure and to discuss the role of these TLRs in DNP progression.Patients and Methods: In this study, blood samples were obtained from type 2 diabetic patients with or without renal failure, and patients with non-diabetic renal failure were compared to healthy controls. All participants were tested for analysis of fasting plasma glucose and serum insulin, kidney function tests, C-reactive protein (CRP), and proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6) as well as expression of TLR2 and TLR4 in peripheral blood (PB). Statistical analysis of data was done by using SPSS.Results: Diabetic patients with renal failure exhibited significant increase in TLR2, TLR4 mRNA expression in PB in comparison with normal subjects, diabetic patients without renal failure and non-diabetic patients with renal failure. Both diabetic patients with or without kidney failure and non-diabetic patients with renal failure had increased TLR2 and TLR4 mRNA expression in association with increased levels of proinflammatory cytokines (TNF-α, IFN-γ, and IL-6) compared to normal subjects. The diabetic patients with kidney failure exhibited the highest elevation of TLRs, Th1 cytokines and CRP in association the highest record of insulin resistance.Conclusion: Toll-like receptor 2 and Toll-like receptor 4 increased expression and Th2 cytokines may have an important role in the progression of DNP and deteriorations in insulin resistance in type 2 diabetic patients. Therefore, TLR2 and TLR4 may be a promising therapeutic target to prevent or retard DNP in type 2 diabetic patients.

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