Fatigue and oxidative stress response to physical activity in type 2 diabetic patients

Physical activity (PA) and exercise is known to have a positive impact on a variety of variables pertinent to diabetes and cardiovascular disease. The aims of this study were to investigate the effects of physical activity on fatigue scores, oxidative stress, and glycemic control variables of individuals with type 2 diabetes mellitus (T2DM). Seventy-five subjects diagnosed with T2DM for more than 5 years aged 18–65 years participated in this study. The participants classified according to energy expenditure into, physically inactive [≤500 metabolic equivalents (METs)-min/week, n?=?25], moderate PA (500–2500 METs-min/week, n?=?25), and PA (≥2500 METs-min/week, n?=?25). The Global Physical Activity Questionnaire (GPAQ) version 2.0 was used to classify physical activity. The multidimensional checklist individual strength questionnaire (CIS20r) was used to measure chronic fatigue. Blood glucose was measured using a glucose oxidase and peroxidase (GOD-POD) colorimetric method. HbA1c was measured using a commercial kit. Serum insulin level was determined using an ELISA. Analysis of oxidative stress parameters including malonaldehyde (MDA) and total antioxidant capacity (TAC) was done. To test differences between severely fatigued and healthy subjects, an independent t test was performed. Spearman correlations were used to assess correlations between fatigue severity score and disease-related and psychosocial factors. A level of significance was set at p?<?0.05. The results showed a significant reduction of fasting blood sugar, glycosylated hemoglobin, fasting insulin, and MDA along with significant increase in TAC activity in the participants with moderate PA (P?<?0.05) and PA (P?<?0.01), respectively. In relation to CIS-fatigue measurements, about 33 % of the study population (n?=?25) had a CIS score above the cutoff score of 37 with 59.5 mean CIS score, and 67 % of the study population (n?=?50) had CIS score below the cutoff 37; they were classified into heightened fatigue (score 27–35) and healthy (score ≤27). There was a significant correlation between the reduction of diabetic related variables, BMI, PA status, and CIS-fatigue score analyses in T2DM patients. CIS-fatigue scores correlated positively with diabetic related variables and negatively with PA, BMI, and TAC activity. PA plays a vital role in improving CIS-fatigue score in type 2 diabetic patients via reducing oxidative stress and diabetic related variables.     

Enhancement of high glucose‐induced PINK1 expression by melatonin stimulates neuronal cell survival: Involvement of MT2/Akt/NF‐κB pathway

Hyperglycemia is a representative hallmark and risk factor for diabetes mellitus (DM) and is closely linked to DM‐associated neuronal cell death. Previous investigators reported on a genome‐wide association study and showed relationships between DM and melatonin receptor (MT), highlighting the role of MT signaling by assessing melatonin in DM. However, the role of MT signaling in DM pathogenesis is unclear. Therefore, we investigated the role of mitophagy regulators in high glucose‐induced neuronal cell death and the effect of melatonin against high glucose‐induced mitophagy regulators in neuronal cells. In our results, high glucose significantly increased PTEN‐induced putative kinase 1 (PINK1) and LC‐3B expressions; as well it decreased cytochrome c oxidase subunit 4 expression and Mitotracker? fluorescence intensity. Silencing of PINK1 induced mitochondrial reactive oxygen species (ROS) accumulation and mitochondrial membrane potential impairment, increased expressions of cleaved caspases, and increased the number of annexin V‐positive cells. In addition, high glucose‐stimulated melatonin receptor 1B (MTNR1B) mRNA and PINK1 expressions were reversed by ROS scavenger N‐acetyl cysteine pretreatment. Upregulation of PINK1 expression in neuronal cells is suppressed by pretreatment with MT₂ receptor‐specific inhibitor 4‐P‐PDOT. We further showed melatonin stimulated Akt phosphorylation, which was followed by nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) phosphorylation and nuclear translocation. Silencing of PINK1 expression abolished melatonin‐regulated mitochondrial ROS production, cleaved caspase‐3 and caspase‐9 expressions, and the number of annexin V‐positive cells. In conclusion, we have demonstrated the melatonin stimulates PINK1 expression via an MT₂/Akt/NF‐κB pathway, and such stimulation is important for the prevention of neuronal cell apoptosis under high glucose conditions.     

Persistent serpentine supravenous hyperpigmented eruption associated with docetaxel

Various mucocutaneous reactions have been reported with the use of systemic docetaxel. We describe a 47-year-old man who developed a persistent serpentine supravenous hyperpigmented eruption (PSSHE), beginning at the site of docetaxel injection and spreading along the superficial venous network in the anterior aspect of the right forearm and distal arm. The eruption occurred after the first infusion of docetaxel following insufficient venous washing. A second infusion was administered through a vein in the other forearm, but this time, abundant venous washing was performed and a similar eruption did not occur. To our knowledge, this is the second report of docetaxel-induced supravenous discoloration and we discussed the terminology and mechanism of this unique reaction.