Palmitate induces reactive oxygen species production and β-cell dysfunction by activating nicotinamide adenine dinucleotide phosphate oxidase through Src signaling.

[Aims/Introduction]Chronic hyperlipidemia impairs pancreatic β-cell function, referred to as lipotoxicity. We have reported an important role of endogenous reactive oxygen species (ROS) overproduction by activation of Src, a non-receptor tyrosine kinase, in impaired glucose-induced insulin secretion (GIIS) from diabetic rat islets. In the present study, we investigated the role of ROS production by Src signaling in palmitate-induced dysfunction of β-cells. [Materials and Methods]After rat insulinoma INS-1D cells were exposed to 0.6 mmol/L palmitate for 24 h (palmitate exposure); GIIS, ROS production and nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity were examined with or without exposure to10 μmol/L 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), a Src inhibitior, for 30 or 60 min. [Results]Exposure to PP2 recovered impaired GIIS and decreased ROS overproduction as a result of palmitate exposure. Palmitate exposure increased activity of NOX and protein levels of NOX2, a pathological ROS source in β-cells. Palmitate exposure increased the protein level of p47phox, a regulatory protein of NOX2, in membrane fraction compared with control, which was reduced by PP2. Transfection of small interfering ribonucleic acid of p47phox suppressed the augmented p47phox protein level in membrane fraction, decreased augmented ROS production and increased impaired GΙIS by palmitate exposure. In addition, exposure to PP2 ameliorated impaired GIIS and decreased ROS production in isolated islets of KK-Ay mice, an obese diabetic model with hyperlipidemia. [Conclusions]Activation of NOX through Src signaling plays an important role in ROS overproduction and impaired GΙIS caused by chronic exposure to palmitate, suggesting a lipotoxic mechanism of β-cell dysfunction of obese mice

miR-22 represses cancer progression by inducing cellular senescence

The microRNA miR-22 targets CDK6, SIRT1, and Sp1—genes involved in regulation of the senescence program—to suppress cell growth and proliferation

Conflict Minerals and Corporate Social Responsibilities in Sweden : How do Swedish companies respond to the conflict minerals issue and what are the challenges?

This study focuses on one of the emerging issues in Corporate Social Responsibility (CSR), “conflict minerals”. The discussion of the “conflict minerals” issue is that the trade of “conflict minerals”, originating from the eastern Democratic Republic of the Congo (DRC), helps to finance conflicts characterized by extreme violence including killing and rape, therefore, the downstream companies which indirectly buy these minerals should take actions (Global Witness, 2010).This study first seeks to provide an overview of the Swedish companies’ progress on the conflict minerals issue through desktop research, and later tries to find out the driving forces, the measures and the existing challenges related to the conflict minerals issue through case studies. In the case studies, interviews were carried out with Sony Ericsson and Atlas Copco. The results of the study show that most companies studied in the six industries have not addressed the conflict minerals issue while companies in the electronic industry has made the most progress on conflict minerals in Sweden. In the case studies, the results present that external pressure is one of the major driving forces for both companies, and Sony Ericsson have taken several measures which seem to be aligned with supply chain risk management approach and OECD DD Guidance. In addition, both companies have tried to integrate conflict mineral management into existing supply chain management. The challenges are different depending on the progress of the companies.The study contributes to providing a better understanding of the current situation surrounding the conflict minerals issue in Sweden and to elaborating examples of the measures and the existing challenges

Peak Oxygen Uptake and Respiratory Function in Persons with Spinal Cord Injury

This study investigated the association between peak oxygen uptake (peak Vo_2) during arm cranking exercise and respiratory function in paraplegics. Fourteen male paraplegics were recruited for the present study. The subjects were grouped according to the level of injury into the HL (Th3-Th8) and LL (Th11-L3) group. Prior to the maximal test, pulmonary function, including vital capacity (VC) and residual volume (RV), was measured in the sitting position. Mean peak Vo_2 in the LL group (1662 mlロin^-1) was significantly greater than that in the IIL group (1357 mlロin^-1), corresponding to 82% of that in the LL group (P ≦0.05). Inrespiratory function, the HL group showed marked restrictive impairment of ventilatory function. That is, VC and RV were significantly lower in the HL group than in the LL group (P≦0.05). The reduction in VC and RV is related to the degree of loss of control in respiratory functioning muscle mass. However, there was no clear-cut correlation between respiratory function and peak V02 expressed as a function of body mass (mlkg^-1 min^-1). In addition, a multiple linear regression analysis revealed that RV and VC were not associated with peak V0_2 (mlロin^-1) in contrast to the importance of body mass. It seems reasonable to conclude from these results that respiratory function is not an important factor in determining peak Vo_2 in the paraplegi

Sex Differences in Interrelationships between Percent Body Fat (%Fat) and Waist-to-Hip Ratio (WHR) in Healthy Male and Female Adults

The purpose of the present study was to investigate sexual differences in relationships among percent body fat (%Fat), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), abdominal circumference to stature ratio (ASR), body mass Index (BMI) and skinfold thicknesses in healthy male and female adults. Subjects were 64 males and 65 females, aged 22-60. Body density was measured by under \vater weighing and by skinfold anthropometry. Mean %Fat was 15.6% in males and 23.9% in females. Mean WHR was 0.83 in males and 0.72 in females. The correlation between %Fat and WHR was not significant in females (r= -0.l04) but was significant in males (r= 0.631, p 0.001). Highly significant correlations were obtained among %Fat, WSR, ASR, BMI, and sum of eight skinfolds in both sexes

Oral Administration of Apple Procyanidins Ameliorates Insulin Resistance via Suppression of Pro-inflammatory Cytokines Expression in Liver of Diabetic ob/ob Mice

Genetic factors are important determinants of the onset and progression of diabetes mellitus. Numerous susceptibility genes for type 2 diabetes, including potassium voltage-gated channel, KQT-like subfamily Q, member1 (KCNQ1), have been identified in humans by genome-wide analyses and other studies. Experiments with genetically modified mice have also implicated various genes in the pathogenesis of diabetes. However, the possible effects of the parent of origin for diabetes susceptibility alleles on disease onset have remained unclear. Here, we show that a mutation at the Kcnq1 locus reduces pancreatic β-cell mass in mice by epigenetic modulation only when it is inherited from the father. The noncoding RNA KCNQ1 overlapping transcript1 (Kcnq1ot1) is expressed from the Kcnq1 locus and regulates the expression of neighboring genes on the paternal allele. We found that disruption of Kcnq1 results in reduced Kcnq1ot1 expression as well as the increased expression of cyclin-dependent kinase inhibitor 1C (Cdkn1c), an imprinted gene that encodes a cell cycle inhibitor, only when the mutation is on the paternal allele. Furthermore, histone modification at the Cdkn1c promoter region in pancreatic islets was found to contribute to this phenomenon. Our observations suggest that the Kcnq1 genomic region directly regulates pancreatic β-cell mass and that genomic imprinting may be a determinant of the onset of diabetes mellitus