Acetylation and insulin resistance: a focus on metabolic and mitogenic cascades of insulin signaling.

Insulin resistance is associated with an increased risk of several metabolic disorders including type 2 diabetes, hypertension and cardiovascular diseases. Advances over the last decade have expanded our understanding of the molecular mechanisms underlying insulin resistance; however, many details of the mechanisms causing insulin resistance remain unknown. Recently, attention has shifted toward the role of epigenetics in insulin resistance. In this regard, acetylation of the histone tails has been widely investigated for its role in influencing both metabolic and mitogenic cascades of insulin signaling. More specifically, histone acetyltransferases and histone deacetylases, as major modulators of chromatin accessibility and gene expression, have been studied to determine a possible interconnectivity between the special effects of lysine acetylation status and tyrosine phosphorylation networks on the target proteins of downstream pathways involved in both metabolic and mitogenic cascades of insulin signaling. There is accumulating evidence for the post-translational modification effects of IGFR, InsR, IRS1/2, PI3K, Akt, GLUT4, FoxO, PGC-1α, PPAR, AMPK and MAPKs on insulin resistance and glucose homeostasis. In this paper, we review the importance of acetylation of these factors in the regulation of insulin signaling and glucose metabolism, with a primary focus on the target proteins of downstream signaling of insulin. We also provide an update on the interplay between epigenetic modification and the cellular genome in the context of insulin signaling and describe the possible effect of the environment on this epigenetic regulation.

Stability of Thirty-Four Analytes in Blood Samples of Diabetic Patients.

BACKGROUND: Storage of biological samples may alter the values of an analyte compared to that of initial measurement. Therefore, an optimal storage condition for every analyte in serum and whole blood samples needs to be determined. The aim of this study was to investigate stability of 34 analytes at different time and temperature conditions of storage. METHODS: This study assessed the stability of hematological parameters in whole blood sample and common biochemical analytes in serum of 40 diabetic patients after 24 and 48 hours in 2 - 8°C and after 30 days in -20°C of sample collection. The mean values of analytes in 3 different storage conditions were measured and compared to that of initial values. RESULTS: Most of the examined biochemical analytes and hematological parameters were stable up to 48 hours at 2 - 8°C after sample collection. Most of the negative changes were negligible but PTH level dramatically decreased after 48 hours in 2 - 8°C. In addition, although a clear increase in the concentration of triglycerides, Cr, Urea, T4, and 25-OH vitamin D3 was observed, it was not significant. Furthermore, a statistically significant difference was observed in the values of ALT, Ca, and T4 among the different conditions of storage. Also, values of HbA1c did not show any significant statistical changes among the 3 different conditions of storage. CONCLUSIONS: Taken together, it seems that most of the analytes in the serum of diabetic patients as well as HbA1c are stable up to 30 days of storage.

The role of microRNAs in the regulation of insulin signaling pathway with respect to metabolic and mitogenic cascades: A review.

Insulin resistance (IR) is a shared pathological condition among type 2 diabetes, obesity, cardiovascular disease, and other metabolic disorders. It is growing significantly all over the world and consequently, a substantial effort is needed for developing the potential novel diagnostics and therapeutics. An insulin signaling pathway is tightly modulated by different mechanisms including the epigenetic modifications. Today, a deal of great attention has been shifted towards the regulatory role of noncoding RNAs on target proteins of the insulin signaling pathway. Noncoding RNAs are a major area of the epigenetics which control gene expression at the posttranscriptional levels and include a large class of microRNAs (miRNAs). With this in view, many studies have implicated the mediatory effects of miRNAs on the downstream metabolic and mitogenic proteins of the insulin signaling pathway. Since providing new biomarkers for the early diagnosis of IR and related metabolic traits are very significant, we intended to review the possible role of miRNAs in the regulation of the insulin signaling pathway, with a primary focus on the downstream target proteins of the metabolic and mitogenic cascades.

The Effect of Blood Sample Storage Conditions on HbA1c Concentration.

BACKGROUND: HbA1c concentration is an indicator of the development of long-term complications in diabetic pa-tients. Different sample storage conditions could affect HbA1c values and consequently, clinician's diagnosis. In this study, we studied the effects of various temperatures of storage over time on HbA1c results. METHODS: A total of 40 fresh whole blood samples with various levels of HbA1c were selected for separate HbA1c measurements at three different temperatures (-20°C, 4°C, and 25°C) on subsequent days (0, 7, 14, and 21 days af-ter sample collection) with Cobas Integra 400 assays (Roche Diagnostics, Mannheim Germany). RESULTS: The value of HbA1c at initial measurement (7.05 ± 1.45) was insignificantly higher than results of temper-ature of -20°C and 4° but compared to results at the temperature of 25°C, (6.08% ± 0.86 % after day 7, 5.52% ± 0.80 after day 14, 4.81 % ± 0.66 after day 21) values of initial measurements were significantly higher. CONCLUSIONS: We concluded that the refrigerator or freezer storage temperature is applicable for the measurement of HbA1c by Cobas Integra 400 without adverse effects on the stability of samples on subsequent days.

Comparison of glomerular filtration rate estimation using Jaffé and enzymatic creatinine assays in diabetic patients.

BACKGROUND: Diabetic kidney disease (DKD) develops an end-stage renal failure and is a major cause of death in diabetic patients. A GFR below 60 ml/min per 1.73 m2 is one of the main markers of DKD. Therefore, the development of an accurate test for diagnosis and monitoring of the mentioned disease would be essential. Here, we examined the impacts of two different kits with different methods for creatinine measurement on the GFR values. METHODS: Blood samples were collected from 80 diabetic patients referring to the clinical laboratory. The levels of serum creatinine were assessed using Jaffé and enzymatic assays by kits from two different manufacturers. Then to assess the eGFR levels, the MDRD equation was used. Further descriptive parameters of both methods and correlation of methods were also calculated. RESULTS: Descriptive analysis of the data demonstrates a slight increase in the serum creatinine measured by Jaffé assay which leads to a substantial decrease in the levels of eGFR compared to the eGFR calculated by the enzymatic assay. Moreover, eGFR over 60 mL/min/1.73 m 2 in enzymatic assay was observed in 27.5% of participants while eGFR of the same participants was below 60 mL/min/1.73 m 2 when it was measured by Jaffé method. Consequently, 27.5% positive discordant cases were reported by Jaffé assay followed by misclassifying them as DKD patients compared with the enzymatic assay. CONCLUSION: While using Jaffé assay, a low level of eGFR is observed which generates more misclassification into the DKD group and demands to an inclusive consideration by physicians in order to diagnose and monitor the DKD patients.