Insulin reduces endoplasmic reticulum stress-induced apoptosis by decreasing mitochondrial hyperpolarization and caspase-12 in INS-1 pancreatic ß-cells.

Pancreatic ß-cell mass is a critical determinant of insulin secretion. Severe endoplasmic reticulum (ER) stress causes ß-cell apoptosis; however, the mechanisms of progression and suppression are not yet fully understood. Here, we report that the autocrine/paracrine function of insulin reduces ER stress-induced ß-cell apoptosis. Insulin reduced the ER-stress inducer tunicamycin- and thapsigargin-induced cell viability loss due to apoptosis in INS-1 ß-cells. Moreover, the effect of insulin was greater than that of insulin-like growth factor-1 at physiologically relevant concentrations. Insulin did not attenuate the ER stress-induced increase in unfolded protein response genes. ER stress did not induce cytochrome c release from mitochondria. Mitochondrial hyperpolarization was induced by ER stress and prevented by insulin. The protonophore/mitochondrial oxidative phosphorylation uncoupler, but not the antioxidants N-acetylcysteine and α-tocopherol, exhibited potential cytoprotection during ER stress. Both procaspase-12 and cleaved caspase-12 levels increased under ER stress. The caspase-12 inhibitor Z-ATAD-FMK decreased ER stress-induced apoptosis. Caspase-12 overexpression reduced cell viability, which was diminished in the presence of insulin. Insulin decreased caspase-12 levels at the post-translational stages. These results demonstrate that insulin protects against ER stress-induced ß-cell apoptosis in this cell line. Furthermore, mitochondrial hyperpolarization and increased caspase-12 levels are involved in ER stress-induced and insulin-suppressed ß-cell apoptosis.

Circadian phase advances in children during camping life according to the natural light-dark cycle.

BACKGROUND: It is known that the circadian rhythm phase in adults can be advanced in a natural light-dark cycle without electrical lighting. However, the effect of advanced sleep-wake timing according to the natural light-dark cycle on children's circadian phase is unclear. We investigated the effects of approximately 2 weeks of camping life with little access to artificial lighting on children's circadian phases. We also conducted an exploratory examination on the effects of wake time according to natural sunrise time on the manner of the advance of their circadian phases. METHODS: Twenty-one healthy children (mean ± SD age, 10.6 ± 1.4 years) participated in a camping program with wake time (4:00) being earlier than sunrise time (EW condition), and 21 healthy children (10.4 ± 1.1 years) participated in a camping program with wake time (5:00) being almost matched to sunrise time (SW condition). Salivary dim light melatonin onset (DLMO) before the camping program and that after approximately 2 weeks of camping were compared. RESULTS: DLMO was advanced by approximately 2 h after the camping program compared with the circadian phase in daily life in both conditions. In addition, the advances in DLMO were significantly correlated with mid-sleep points before the camp in both conditions (EW: r = 0.72, p < 0.01, SW: r = 0.70, p < 0.01). These correlations mean that the phase advance was greater for the children with delayed sleep habits in daily life. Furthermore, in the EW condition, mean DLMO after the camp (18:09 ± 0:33 h) was earlier than natural sunset time and there was no significant decrease in interindividual variability in DLMO. On the other hand, in the SW condition, mean DLMO after the camp (18:43 ± 0:20 h) matched natural sunset time and interindividual variability in DLMO was significantly lower than that before the camp. CONCLUSIONS: Camping with advanced sleep and wake timing under natural sunlight advances children's circadian phases. However, DLMO earlier than sunset in an early waking condition may lead to large interindividual variability in the circadian rhythm phase.

Melatonin suppression and sleepiness in children exposed to blue-enriched white LED lighting at night.

Light-induced melatonin suppression in children is reported to be more sensitive to white light at night than that in adults; however, it is unclear whether it depends on spectral distribution of lighting. In this study, we investigated the effects of different color temperatures of LED lighting on children's melatonin secretion during the night. Twenty-two healthy children (8.9 ± 2.2 years old) and 20 adults (41.7 ± 4.4 years old) participated in this study. A between-subjects design with four combinations, including two age groups (adults and children) and the two color temperature conditions (3000 K and 6200 K), was used. The experiment was conducted for two consecutive nights. On the first night, saliva samples were collected every hour under a dim light condition (<30 lx). On the second night, the participants were exposed to either color temperature condition. Melatonin suppression in children was greater than that in adults at both 3000 K and 6200 K condition. The 6200 K condition resulted in greater melatonin suppression than did the 3000 K condition in children (P < 0.05) but not in adults. Subjective sleepiness in children exposed to 6200 K light was significantly lower than that in children exposed to 3000 K light. In children, blue-enriched LED lighting has a greater impact on melatonin suppression and it inhibits the increase in sleepiness during night. Light with a low color temperature is recommended at night, particularly for children's sleep and circadian rhythm.