No evidence for change in expression of TBC1D1 and TBC1D4 genes in cultured human adipocytes stimulated by myokines and adipokines.

TBC1D1 and TBC1D4 proteins play analogous, but not identical role in governing insulin-signalling pathway. Little is known about changes in expression levels of TBC1D1 and TBC1D4 genes in mammals, including humans. Number of factors were studied, but data remain controversial. The aim of this study was to evaluate the effect of selected cytokines, adipokines and myokines with known or putative insulin sensitivity regulation activity (adiponectin, irisin, omentin, interleukin 6, leptin, resistin, and tumour necrosis factor) on TBC1D1 and TBC1D4 expression levels in cultured differentiated human adipocytes. No significant differences were found between the adipocytes treated with different stimuli and this effect was determined not dose dependent. It is reasonable to conclude that relative shortage of data showing no change in TBC1D1 and TBC1D4 from literature results from publication bias; therefore, our finding provides additional insight into the role of both genes.

The HD-OCT Study May Be Useful in Searching for Markers of Preclinical Stage of Diabetic Retinopathy in Patients with Type 1 Diabetes.

The aim of the study was to analyze the thickness of individual retinal layers in patients with type 1 diabetes (T1D) in comparison to the control group and in relation to markers of diabetes metabolic control. The study group consisted of 111 patients with an average of 6-years of T1D duration. The control group included 36 gender- and age-matched individuals. In all patients optical coherence tomography (OCT) study was performed using HD-OCT Cirrus 5000 with evaluation of optic nerve head (ONH) parameters, thickness of retinal nerve fiber layer (RNFL) with its quadrants, macular full-thickness parameters, ganglion cells with inner plexus layer (GCIPL) and choroidal thickness (CT). Lower disc area value was observed in the study group as compared to controls (p = 0.0215). Negative correlations were found both between age at examination and rim area (R = -0.28, p = 0.0007) and between superior RNFL thickness and duration of diabetes (R = -0.20, p = 0.0336). Positive correlation between center thickness and SD for average glycemia (R = 0.30, p = 0.0071) was noted. Temporal CT correlated positively with age at examination (R = 0.21, p = 0.0127). The selected parameters the HD-OCT study may in the future serve as potential markers of preclinical phase of DR in patients with T1D.

Serum uric acid concentration is associated with early changes of glomerular filtration rate in patients with diabetes type 1 without increased albumin excretion.

UNLABELLED: The early loss of renal function in patients with type 1 diabetes may begin before proteinuria. Only 30% of patients with diabetes manifest overt proteinuria. According to the previous studies, increased urinary albumin excretion, which is considered a classic marker of progression of diabetic kidney disease, can regress to normal urine albumin excretion. The current studies conducted in patients with type 1 diabetes without increased urine albumin excretion showed that the uric acid concentration was an independent factor for the development of diabetic kidney disease. The aim of study was to assess the impact of uric acid concentration and to identify risk factors of the early glomerular filtration loss in patients with type 1 diabetes and normal urinary albumin excretion. MATERIALS AND METHODS: 147 patients (61 women and 86 men) with type 1 diabetes without increased urine albumin excretion were analysed. GFR (gromerular filtration rate) was estimated based on the serum cystatin C concentration. Centile charts were used to determine the variation of uric acid concentration depending on GFR and gender. RESULTS: The mean value of the filtration rate for the study group was 117 ml/min/m2. The uric acid level above 90th percentile in relation to GFR was diagnosed in 8.2% of women and 0% of men, between 90th and 50th percentile in 44.3 % of women and 5.8% of men and below 50th percentile in 47.5% of women and 94.2% of men. Contrary to men in women higher serum acid concentration was strongly associated with higher glomerular filtration rate. Hyperfiltraion was diagnosed in 15 of women and 19 of men. CONCLUSIONS: The high normal uric acid concentration in women with type 1 diabetes might play a crucial role in development of hyperfiltration.

The effect of uremia and hemodialysis on caspase-1 and caspase-3 activity in neutrophils.

BACKGROUND: Neutrophils in uremia maintain chronic inflammation, which contributes to malnutrition and immunity disorders. The influence of hemodialysis on the life span of neutrophils is unclear, although many authors postulate its apoptotic effect. Erythropoietin (EPO) is an antiapoptotic factor for various cells. We investigated factors possibly interfering in apoptosis of neutrophils in hemodialysis (HD) patients, such as HD session, parathormone (PTH), dose of EPO, inflammation and nutrition. SUBJECTS AND METHODS: Twenty HD patients and ten healthy controls were donors of neutrophils. We evaluated caspase-1 and caspase-3 activities, related to apoptosis of neutrophils, before and after a 4-hour HD session with cuprophane or polysulphone dialyzer. We measured serum concentrations of C-reactive protein, cholesterol, albumin, prealbumin and transferrin. Time of dialysis treatment, PTH level and dose of EPO were also evaluated. RESULTS: We observed a significant increase in caspase-1 activity and decrease in caspase-3 activity in neutrophils after HD with cuprophane, but not with polysulphone. Caspase-1 activity correlated positively with EPO dose and negatively with PTH level. Caspase-3 correlated negatively with the time of dialysis treatment. No correlation between caspase activity and markers of inflammation or nutrition was noticed. CONCLUSIONS: The results suggest that HD with bioincompatible cuprophane may prolong the life span of neutrophils due to the intense inflammatory reaction and high activity of caspase-1. Time of dialysis treatment, PTH level and EPO dose potentially influence the life span of neutrophils. PTH seems to have a proapoptotic effect of neutrophils, while EPO is an antiapoptotic factor.

[Caspases--a new target in inflammation and cancer therapy?]. / Kaspazy--nowy cel w terapii przeciwzapalnej i przeciwnowotworowej?

The family of caspases - intracellular cysteine proteases - comprises enzymes engaged in inflammatory response or cell apoptosis. The activity of caspases is a determinant for the life span of many cells. Defects in activity of some members of the caspase family can be related to neurodegenerative disorders, autoimmune diseases and cancer. The current knowledge of the structure, substrate specificity and function of caspases encourages interfering with caspase signaling and to pharmacological manipulation of the cell apoptosis.

[Caspases--structure and function]. / Kaspazy--struktura i funkcja.

Caspases, a unique family of cysteine proteases, are involved in both the initiation and execution phase of cell apoptosis. They also play a vital role in the inflammatory responses. Caspases exist in cells as inactive zymogenes and undergo a cascade activation, which inevitably leads to the cell death. These highly specialized enzymes create the network of intracellular signaling through proteolysis. The network regulates the function and the life span of cells in physiological and pathological states.