Both type I and II IFN induce insulin resistance by inducing different isoforms of SOCS expression in 3T3-L1 adipocytes.

Although elevation of the blood glucose level is a causal adverse effect of treatment with interferon (IFN), the precise underlying molecular mechanism is largely unknown. We examined the effects of type I and type II IFN (IFN-ß and IFN-γ) on insulin-induced metabolic signaling leading to glucose uptake in 3T3-L1 adipocytes. IFN-ß suppressed insulin-induced tyrosine phosphorylation of IRS-1 without affecting its expression, whereas IFN-γ reduced both the protein level and tyrosine phosphorylation. Although both IFNs stimulated phosphorylation of STAT1 (at Tyr(701)) and STAT3 (at Tyr(705)) after treatment for 30 min, subsequent properties of induction of the SOCS isoform were different. IFN-ß preferentially induced SOCS1 rather than SOCS3, whereas IFN-γ strongly induced SOCS3 expression alone. In addition, adenovirus-mediated overexpression of either SOCS1 or SOCS3 inhibited insulin-induced tyrosine phosphorylation of IRS-1, whereas the reduction of IRS-1 protein was observed only in SOCS3-expressed cells. Notably, IFN-ß-induced SOCS1 expression and suppression of insulin-induced tyrosine phosphorylation of IRS-1 were attenuated by siRNA-mediated knockdown of STAT1. In contrast, adenovirus-mediated expression of a dominant-negative STAT3 (F-STAT3) attenuated IFN-γ-induced SOCS3 expression, reduction of IRS-1 protein, and suppression of insulin-induced glucose uptake but did not have any effect on the IFN-ß-mediated SOCS1 expression and inhibition of insulin-induced glucose uptake. Interestingly, pretreatment of IFN-γ with IL-6 synergistically suppressed insulin signaling, even when IL-6 alone had no significant effect. These results indicate that type I and type II IFN induce insulin resistance by inducing distinct SOCS isoforms, and IL-6 synergistically augments IFN-γ-induced insulin resistance by potentiating STAT3-mediated SOCS3 induction in 3T3-L1 adipocytes.

Development of disaster pamphlets based on health needs of patients with chronic illnesses.

The aim of this research was to develop a pamphlet that would enable patients with diabetes, rheumatic diseases, chronic respiratory disease, and dialysis treatment to be aware of changes in their physical conditions at an early stage of a disaster, cope with these changes, maintain self-care measures, and recover their health. Illness-specific pamphlets were produced based on disaster-related literature, news articles, surveys of victims of the Great Hanshin-Awaji Earthquake Disaster and Typhoon Tokage, and other sources. Each pamphlet consisted of seven sections-each section includes items common to all illnesses as well as items specific to each illness. The first section, "Physical Self-Care", contains a checklist of 18 common physical symptoms as well as symptoms specific to each illness, and goes on to explain what the symptoms may indicate and what should be done about them. The main aim of the "Changes in Mental Health Conditions" section is to detect posttraumatic stress disorder (PTSD) at an early stage. The section "Preventing the Deterioration of Chronic Illnesses" is designed to prevent the worsening of each illness through the provision of information on cold prevention, adjustment to the living environment, and ways of coping with stress. In the sections, "Medication Control" and "Importance of Having Medical Examinations", spaces are provided to list medications currently being used and details of the hospital address, in order to ensure the continued use of medications. The section, "Preparing for Evacuations" gives a list of everyday items and medical items needed to be prepared for a disaster. Finally, the "Methods of Contact in an Emergency" section provides details of how to use the voicemail service. The following content-specific to each illness also was explained in detail: (1) for diabetes, complications arising from the deterioration of the illness, attention to nutrition, and insulin management; (2) for rheumatic diseases, a checklist of factors indicating the worsening of the illness and methods of coping with stress; (3) for chronic respiratory disease, prevention of respiratory infections and management of supplemental oxygen; and (4) for patients requiring dialysis, conditions of dialysis (such as dry weight, dialyzer, number of dialysis treatments, and dialysis hours) and what to do if a disaster occurs during dialysis. It is expected that these pamphlets will be useful to patients with chronic illnesses, and will be used to prepare for disasters, thereby helping the patients cope with the unusual situation that during a disaster and recover as soon as possible.

An investigation of the effect of social reciprocity, social anxiety, and letter fluency on communicative behaviors in adults with autism spectrum disorder.

In recent years, research focusing on childhood has reported that communication difficulties in autism spectrum disorder (ASD) are related to the social reciprocity difficulties inherent to ASD, as well as severe social anxiety and decreased verbal fluency. However, there have been no reports regarding these correlations and causal relationships in adulthood. The aim of this study was to reveal the effects of social reciprocity, social anxiety, and letter fluency on communicative behaviors in adults with ASD (n = 33, aged 18-43 years, mean age = 27.88 years) and to compare these to typically developing (TD) adults (n = 35, 19-40 years, mean age = 28.03 years). We validated a model using structural equation modeling in which social reciprocity not only directly affected communicative behaviors, but also indirectly affected communicative behaviors mediated by social anxiety and verbal fluency. The results of the structural equation modeling showed that communicative behaviors patterns differed between the ASD and TD groups, as the ASD group had high goodness of fit with the hypothesis model while the TD group had low goodness of fit. These findings signify that in ASD, in addition to problems in social reciprocity, social anxiety (fear) is a risk factor for worsening communicative behaviors difficulties.

Sex Differences in White Matter Pathways Related to Language Ability.

Evidence from functional imaging studies points to a role for gender in language ability. However, recent studies suggest that sex differences in the neural basis of language are still unclear, reflecting a complex interaction between sex and language ability. We used diffusion weighted magnetic resonance imaging and global probabilistic tractography to investigate white matter (WM) pathways between 32 male and 35 age- and IQ-matched female adult participants in relation to their verbal abilities. Males showed higher fractional anisotropy (FA) in the left anterior thalamic radiations (ATR), right cingulum-angular bundle, right corticospinal tract, bilateral superior longitudinal fasciculus-temporal terminations, bilateral uncinate fasciculus (UNC), and corpus callosum-forceps minor when compared with the female group. In contrast, females showed higher radial diffusivity (RD) in the left ATR and left UNC when compared to the male group. The relationship between WM metrics and verbal ability also differed across the two groups: a negative correlation between verbal comprehension index (VCI) and FA as well as axial diffusivity (AD) in left cingulum-cingulate gyrus (CCG) supracallosal bundle in males but not in females; a negative correlation between verbal IQ (VIQ) and FA in the right corticospinal tract (CST), and a positive correlation between VCI and RD in corpus callosum-forceps minor in the female but not in the male group. A direct comparison of these correlation coefficients yielded significant differences between the groups for the VCI-AD and VIQ -FA associations. The findings may reflect sex differences in WM related to language ability.

Physiological changes of Fas expression in peripheral lymphocyte subsets during the menstrual cycle.

We have examined changes in peripheral lymphocyte subsets, and Fas expression in these subsets, during the menstrual cycle. Measurements were made by three-color flow cytometry in the follicular and luteal phases of the menstrual cycle in ten healthy women. The numbers of leukocytes, granulocytes and monocytes were significantly higher in the luteal phase than the follicular phase. The percentage of CD8(+) cells was greater in the luteal phase than the follicular phase. The percentages of Fas(+) cells among T cells and NK cells were higher in the luteal phase than the follicular phase. These findings suggest that the menstrual cycle affects leukocytes, lymphocyte subsets, and Fas expression in these subsets, and that changes in the luteal phase of the menstrual cycle are similar to those in pregnancy.

Cilostazol ameliorates systemic insulin resistance in diabetic db/db mice by suppressing chronic inflammation in adipose tissue via modulation of both adipocyte and macrophage functions.

Cilostazol, an inhibitor of phosphodiesterase 3B, is widely used as an anti-platelet drug in diabetic patients. Recently, cilostazol has been shown to promote preadipocyte differentiation to mature adipocyte and affect glucose homeostasis; therefore, we examined the impact of cilostazol on impaired glucose metabolism in adipose tissues of diabetic db/db mice. Administration of cilostazol at 100-300 mg/kg/day significantly improved glucose tolerance and insulin sensitivity in a dose-dependent manner in db/db mice, whereas these effects were not observed in non-diabetic control mice. Cilostazol reduced the adipocyte size and suppressed mRNA expressions of monocyte chemoattractant protein 1, CD11c, and tumor necrosis factor α (TNFα) in the epididymal fat tissue of db/db mice. As for the cellular mechanism, cilostazol attenuated lipopolysaccharide (LPS)-induced TNFα expression by decreasing the mRNA and protein levels of Toll-like receptor 4 in Raw264.3 macrophages. Cilostazol also effectively ameliorated the TNFα-induced decrease of insulin-stimulated Akt phosphorylation and [(3)H]2-deoxyglucose uptake by suppressing c-Jun N terminal kinase-mediated serine phosphorylation of insulin receptor substrate 1 in 3T3-L1 adipocytes. Importantly, the improvement of impaired insulin signaling was blunted by pretreatment with KT5720, a protein kinase A inhibitor, but not with GW9662, a peroxisome proliferator-activated receptor γ. These results indicate that cilostazol suppressed TNFα production from macrophages and attenuated TNFα-induced chronic inflammation in adipose tissue, leading to the improvement of glucose intolerance and insulin resistance in obese diabetic mice. Thus, the present study reveals an additional benefit in the use of cilostazol in the treatment of patients with type 2 diabetes.

Variation in the 5'-flanking region of the neuropeptide Y2 receptor gene and metabolic parameters.

A previous report describes that neuropeptide Y (NPY)/NPY2 receptor (NPY2R) is involved in stress-induced visceral obesity. This is a report clarifying the effect on metabolic parameters of single nucleotide polymorphisms in the 5'-flanking region of NPY2R gene. Study participants are 317 people (98 men and 219 women, 40-79 years old) undergoing health checkups. The single nucleotide polymorphism typing of rs6857715 and rs6857530 located on the 5'-flanking region of the NPY2R gene was performed using allele-specific polymerase chain reaction method. Serum high-density lipoprotein cholesterol (HDL-C) level was significantly lower in men possessing rs6857715 TT genotype compared with CC and in men possessing rs6857530 GG genotype compared with AA. No significant difference was observed between each genotype and other metabolic parameters including body mass index, waist circumference, systolic and diastolic blood pressure, serum low-density lipoprotein cholesterol, triglyceride, and fasting plasma glucose. The variation in the 5'-flanking region of the NPY2R gene was associated with serum HDL-C level in men and was a predictor for serum HDL-C level independent of sex and serum triglyceride level.

Genetic variations at the CCAAT/enhancer-binding protein delta are associated with metabolic phenotypes in the Japanese population.

BACKGROUND: Expression of CCAAT/enhancer-binding protein delta (C/EBP-delta) gene is enhanced in the early initial stage of adipocyte differentiation. This study is intended to elucidate the association between the genetic variation of C/EBP-delta and metabolic phenotypes. SUBJECTS AND METHODS: Subjects were unselected 52 males and 120 females in Japan, aged 40 to 79 years, who visited a city hygienic center for a health checkup and agreed to participation in the study after giving informed consent. The C/EBP-delta genotypes and metabolic phenotypes were determined. An association study was performed using Pearson's chi(2) tests and logistic regression analyses. RESULTS: Two SNPs in C/EBP-delta gene with minor allele frequency greater than 0.05 were detectable among seven SNPs. Genotype heterozygous for the C and T allele (877C/T) were more prevalent in subjects with dyslipidemia [plasma triglyceride (TG) > or =150 mg/dL and/or plasma high-density lipoprotein-cholesterol (HDL-C) <40 mg/dL] as well as high fasting plasma glucose (FPG; > or =110 mg/dL) than controls (22.5% vs. 7.6%, P = 0.009, and 20.0% vs. 8.4%, P = 0.041, respectively). Moreover, the genotype 877C/T contributed to both dyslipidemia and high FPG independent of age, sex, and visceral obesity. Regarding 394C>G, no association between the genotype and metabolic phenotypes was detected. CONCLUSION: Results suggest that genetic variations in the C/EBP-delta might play a role in some metabolic phenotypes.