BACKGROUND AND AIMS:The incidence of statin-induced new-onset diabetes (NOD) is increasing but its underlying mechanisms remain unclear. We aimed to investigate the effects of various doses of atorvastatin (ATO)-induced autophagy on the development of NOD. METHODS AND RESULTS:The isolated rat islets and MIN6 cells-treated with ATO, exhibited impaired glucose-stimulated insulin secretion, reduced insulin content, and induced apoptosis. Additionally, autophagy was induced at all doses (in vitro: 5, 10, 20 μM; in vivo: 10, 15, 20 mg/kg) in ATO-treated MIN6 cells or western diet (WD)-fed mice. In contrast to normal glucose-tolerant mice administered a low-dose (10 mg/kg) ATO, those treated with high-doses (15 or 20 mg/kg) exhibited impaired glucose tolerance. Furthermore, high-dose ATO-treated mice showed decreased β-cell mass and increased apoptosis compared to that of vehicle-treated mice. We also observed that the number of vesicophagous cells in the pancreas of 20 mg/kg ATO-treated WD-fed mice was higher than in vehicle-treated WD-fed mice. Inhibiting autophagy using 3-methyladenine (3-MA) and siAtg5 improved glucose tolerance in vivo and in vitro by preventing apoptotic β-cell death and restoring insulin granules. CONCLUSION:These results indicate that high doses of ATO induced hyperactivated autophagy in pancreatic cells, leading to impaired insulin storage, decreased cell viability, and reduced functional cell mass, ultimately resulting in NOD development.

OBJECTIVE:This study investigated whether sleep and stress mutually interact to induce changes in white matter integrity.METHODS:Diffusion tensor imaging (DTI) was conducted on 36 participants (male=22, female=14; mean age=38.33±12.78 years). Participants were divided into three groups depending on their sleep quality and stress levels: poor sleepers with stress, poor sleepers without stress, and good sleepers. Sleep quality and stress level were evaluated using the Pittsburgh Sleep Quality Index and the Life Experiences Survey, respectively. Fractional anisotropy (FA) values were calculated employing DTI tractography.RESULTS:After controlling for age and sex, poor sleepers with stress exhibited a lower FA of the left inferior cerebellar peduncle (ICP) than did poor sleepers without stress (t=2.81, p=0.02). Poor sleepers without stress showed a higher FA of the right middle longitudinal fasciculus (MdLF) than did good sleepers (t=3.35, p=0.006).CONCLUSION:The current study reports the effects of sleep, stress, and their interaction on the white matter integrities of the ICP and MdLF. ICP change seems to be associated with sleep disturbances related to stress, while MdLF change would be associated with sleep disturbances unrelated to stress.

Background Dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has been shown to reduce body weight and liver fat content in patients with type 2 diabetes. Family with sequence similarity 3 member A (FAM3A) plays a vital role in regulating glucose and lipid metabolism. The aim of this study was to determine the mechanisms by which dulaglutide protects against hepatic steatosis in HepG2 cells treated with palmitic acid (PA). Methods HepG2 cells were pretreated with 400 μM PA for 24 hours, followed by treatment with or without 100 nM dulaglutide for 24 hours. Hepatic lipid accumulation was determined using Oil red O staining and triglyceride (TG) assay, and the expression of lipid metabolism-associated factor was analyzed using quantitative real time polymerase chain reaction and Western blotting. Results Dulaglutide significantly decreased hepatic lipid accumulation and reduced the expression of genes associated with lipid droplet binding proteins, de novo lipogenesis, and TG synthesis in PA-treated HepG2 cells. Dulaglutide also increased the expression of proteins associated with lipolysis and fatty acid oxidation and FAM3A in PA-treated cells. However, exendin-(9–39), a GLP-1R antagonist, reversed the expression of FAM3A, and fatty acid oxidation-associated factors increased due to dulaglutide. In addition, inhibition of FAM3A by siRNA attenuated the reducing effect of dulaglutide on TG content and its increasing effect on regulation of fatty acid oxidation. Conclusion These results suggest that dulaglutide could be used therapeutically for improving nonalcoholic fatty liver disease, and its effect could be mediated in part via upregulation of FAM3A expression through a GLP-1R-dependent pathway.

Introduction:We investigated the white matter integrity in shift and non-shift workers and its associations with sleep and activity. Methods:Diffusion tensor imaging (DTI) was performed on 61 shift workers and 31 non-shift workers. Their sleep and activity profiles were assessed using the Pittsburgh Sleep Quality Index (PSQI), sleep diaries, and actigraphy. Fractional anisotropy (FA) (a measure of white matter integrity) was calculated using DTI tractography. Results:Shift workers exhibited higher FA values in the bilateral anterior cingulum than did non-shift workers. An increased FA in the right anterior cingulum was correlated with poor sleep quality (ie, a high PSQI score) in shift workers. An increased FA in the right anterior cingulum was also correlated with higher actigraphic activity indices (the mesor and M10 indices) in shift workers. Discussion:The white matter integrity of the anterior cingulum was altered in shift workers, perhaps in association with sleep and activity disturbances.