The clock gene Bmal1 controls inflammatory mediators in rheumatoid arthritis fibroblast-like synoviocytes.

Object: To clarify the involvement of clock genes in the production of inflammatory mediators from RA-FLS, we examined the role of Bmal1, one of the master clock genes.

Methods: RA-FLSs were stimulated with IL-1β (0, 20 ng/mL), IL-6 (0, 20 ng/mL), IL-17 (0, 20 ng/mL), TNF-α (0, 20 ng/mL) or IFN-γ (0, 20 ng/mL) to examine the expression of Bmal1, MMP-3, CCL2, IL-6, IL-7 and IL-15 by qPCR and immunofluorescence staining. After silencing Bmal1, RA-FLSs were stimulated with IL-1β (0, 20 ng/mL), TNF-α (0, 20 ng/mL) or IFN-γ (0, 20 ng/mL) to examine the expressions of inflammatory mediators; MMP-3, CCL2, IL-6 and IL-15 by qPCR, ELISA and immunofluorescence staining.

Exenatide improves hepatocyte insulin resistance induced by different regional adipose tissue.

Obesity is resulted from energy surplus and is characterized by abnormal adipose tissue accumulation and/or distribution. Adipokines secreted by different regional adipose tissue can induce changes in key proteins of the insulin signaling pathway in hepatocytes and result in impaired hepatic glucose metabolism. This study aimed to investigate whether exenatide affects key proteins of IRS2/PI3K/Akt2 signaling pathway in hepatocytes altered by the different regional fat depots.

Reduced gluteofemoral (subcutaneous) fat mass in young Japanese women with family history of type 2 diabetes: an exploratory analysis.

Limited expandability of subcutaneous adipose tissue may be characteristics of first-degree relatives of type 2 diabetes. We tested the hypothesis that family history of type 2 diabetes (FHD) may be associated with reduced peripheral fat mass. Body composition and metabolic variables were compared between 18 and 111 Japanese female collegiate athletes, and between 55 and 148 nonathletes with positive (FHD +) and negative FHD (FHD-), respectively.

Birth weight was associated positively with gluteofemoral fat mass and inversely with 2-h postglucose insulin concentrations, a marker of insulin resistance, in young normal-weight Japanese women.

Introduction: We tested whether birth weight might be associated with gluteofemoral fat mass and insulin sensitivity later in life.

Materials And Methods: Body size trajectory since birth, body composition at age 20, and markers of insulin resistance were measured in 316 Japanese women. A subset of 148 women underwent a 75 g oral glucose tolerance test.

Weight Trajectory Since Birth, Current Body Composition, Dietary Intake, and Glucose Tolerance in Young Underweight Japanese Women.

We studied weight trajectory since birth and dietary intake in Japanese female students majoring in nutrition sciences. Birth weight, adolescent height and weight, current body composition by whole-body dual-energy X-ray absorptiometry, dietary intake, glucose tolerance, lipid profile, and adipokines were cross-sectionally compared between young underweight (body mass index [BMI] <18.5) and normal-weight (BMI ≥18.

Associations of Infant Feeding with Body Composition and Cardiometabolic Health in Young Female University Students.

We assessed the association of infant feeding with body composition and cardiometabolic health at 20 years in a setting where infant feeding is not associated with socioeconomic status. Body size trajectory since birth, current body composition measured using whole-body dual-energy X-ray absorptiometry, and a broad range of cardiometabolic risk factors were compared cross-sectionally among young female university students who were ever breastfed ( = 158, 120 exclusively, and 38 mainly), mixed fed ( = 124), and formula fed ( = 15, 10 mainly, and 5 exclusively) Compared with breastfed and mixed fed women, formula fed women had higher serum total and low-density lipoprotein (LDL) cholesterol although fat mass, fat distribution, fasting glucose, and insulin and high-density lipoprotein cholesterol did not differ. In addition, resting heart rates were higher in formula fed women compared with the other two groups of women although systolic and diastolic blood pressure did not differ.

Serum Orosomucoid Is Associated with Serum Adiponectin, Adipose Tissue Insulin Resistance Index, and a Family History of Type 2 Diabetes in Young Normal Weight Japanese Women.

Introduction: Adipose tissue (AT) expandability may be facilitated by adiponectin and suppressed by orosomucoid, and reduced AT expandability may be associated with first-degree relatives of type 2 diabetes. We tested the hypothesis that orosomucoid may be associated not only with adiponectin and adipose tissue insulin resistance but also with a family history of type 2 diabetes (FHD). Anthropometric and metabolic variables, adipokines, and measures of inflammatory and insulin resistance were cross-sectionally investigated in 153 young normal weight Japanese women.

Association of family history of type 2 diabetes with blood pressure and resting heart rate in young normal weight Japanese women.

Objective: We suggested association of family history of type 2 diabetes (FHD) with microvascular dysfunction, which may cause blood pressure (BP) elevations. We test whether FHD may be associated with higher BP.

Research Design And Methods: Resting BP, heart rates (in beats per minute: bpm), body composition and fasting concentrations of glucose, insulin, leptin and adiponectin were measured in 332 Japanese women aged 18-24 years.

Associations of serum transthyretin with triglyceride in non-obese elderly Japanese women independently of insulin resistance, HDL cholesterol, and adiponectin.

Objective: Studies are limited on the association between serum transthyretin (TTR), a negative acute phase reactant, and triglyceride (TG).

Research Design And Methods: TG, TTR, and insulin resistance-related cardiometabolic variables were measured in 159 fasting and 185 nonfasting community-dwelling elderly women aged 50-96 years. Pearson correlation analysis and then stepwise multiple regression analyses were performed to further identify the most significant variables contributing to the variation of fasting and nonfasting TG.

Reduced Birth Weight, Decreased Early-Phase Insulin Secretion, and Increased Glucose Concentrations after Oral Glucose Tolerance Test in Japanese Women Aged 20 Years with Family History of Type 2 Diabetes.

Introduction: We tested the hypothesis that family history of type 2 diabetes (FHD) is associated with reduced birth weight and reduced insulin secretion later in life.

Materials And Methods: Birth weight, body composition by whole-body dual-energy X-ray absorptiometry, and homeostasis model assessment-insulin resistance were compared between Japanese women aged 20 years with positive ( = 73) and negative ( = 258) FHD. A subsample of 153 women (57 with positive FHD) underwent a 75 g oral glucose tolerance test.

Higher circulating orosomucoid, an acute-phase protein, and reduced glucose-induced insulin secretion in middle-aged Japanese people with prediabetes.

Introduction: Circulating orosomucoid, an acute-phase protein, predicted type 2 diabetes mellitus risk in several Western countries. Here, we assessed serum orosomucoid (ORM) in relation to prediabetes in the Japanese.

Research Design And Methods: Participants consisted of 83 middle-aged Japanese subjects with normal glucose tolerance (NGT), 37 with prediabetes and 4 with newly identified diabetes, whose homeostasis model assessment-insulin resistance (HOMA-IR) averaged 1.

Association of ABC (HbA1c, blood pressure and LDL-cholesterol) goal achievement with visit-to-visit ABC variability and postprandial dysmetabolism in type 2 diabetic patients.

Background And Objectives: Although roles of ABC (HbA1c, blood pressure [BP] and LDL-cholesterol) goal attainment on CVD risk outcomes have been well established, it is less studied whether ABC goal attainment associates with ABC variability, non-traditional risk factors.

Methods And Study Design: Intrapersonal mean levels and standard deviation (SD) of HbA1c, BP and LDL-cholesterol, fasting and post-breakfast plasma glucose (PG) and serum triglyceride (TG) during 12 months were calculated in 168 type 2 diabetes patients (aged 62.3 years, 53.

Determinants and correlates of adipose tissue insulin resistance index in Japanese women without diabetes and obesity.

Introduction: Determinants and correlates of a novel index of adipose tissue insulin resistance (AT-IR) (the product of fasting insulin and free fatty acid concentrations) were investigated in Japanese women without diabetes and obesity.

Research Design And Methods: Cross-sectional associations of AT-IR with fat mass and distribution, and IR-related cardiometabolic variables were examined in 210 young and 148 middle-aged women whose average body mass index (BMI) was <23 kg/m and waist was <80 cm. Multivariate linear regression analyses were used to identify most important determinants of AT-IR.

Decreased arterial distensibility and postmeal hyperinsulinemia in young Japanese women with family history of diabetes.

Introduction: To assess vascular function and characterize insulin secretion using a physiological approach in Japanese women with family history of type 2 diabetes (FHD).

Research Design And Methods: Standardized mixed-meal tests were performed with multiple postprandial glucose, insulin and free fatty acids (FFA) measurements over a 30-120 min period in 31 Japanese women aged 21-24 years. Arterial distensibility was assessed as well.

Higher circulating orosomucoid and lower early-phase insulin secretion in midlife Japanese with slower glucose disposal during oral glucose tolerance tests.

Objective: We examined whether serum orosomucoid, an acute phase protein as with C-reactive protein, in addition to insulin resistance and beta-cell dysfunction, was involved in glucose disposal during oral glucose tolerance tests.

Research Design And Methods: 124 midlife Japanese (65 women, 66% with normal glucose tolerance) received dual-energy X-ray absorptiometry and 75 g oral glucose tolerance tests with multiple postload glucose and insulin measurements. Subjects were divided based on the relationship between postload and fasting glucose.

Associations of ABC (Hemoglobin A1c, Blood Pressure and Low-Density Lipoprotein Cholesterol) Goal Achievement With Chronic Kidney Disease in Type 2 Diabetic Patients With Preserved Kidney Function.

Background: We investigated cross-sectional and prospective associations of ABC (hemoglobin A1c (HbA1c), blood pressure and low-density lipoprotein cholesterol) goal attainment with chronic kidney disease. Cross-sectional association with carotid intima-media thickness (IMT) was evaluated as well.

Methods: Prevalence of low estimated glomerular filtration rate (eGFR < 60 mL/min/1.

Interleukin-6 and tumour necrosis factor-α cooperatively promote cell cycle regulators and proliferate rheumatoid arthritis fibroblast-like synovial cells.

: To elucidate the roles of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in cell cycle regulation and proliferation of rheumatoid arthritis fibroblast-like synovial cells (RA-FLSs). : Under stimulation with IL-6/soluble interleukin-6 receptor (sIL-6R) and TNF-α, we examined the expression of cell cycle regulators [p16, p21, p27, cyclin-dependent kinase-4 (CDK4), CDK6, Cyclin D, Cyclin E, and retinoblastoma protein (pRB)] by quantitative polymerase chain reaction, Western blotting, and immunofluorescence staining. The expression of pRB, with or without 10% foetal bovine serum, was examined by Western blotting.

Association of Age and Anemia With Adiponectin Serum Levels in Normal-Weight Japanese Women.

Background: Adiponectin serum levels are affected by sex, ethnicities, adiposity, age and several pathological conditions such as anemia. The prevalence of hyperadiponectinemia (≥ 20 mg/L) in relation to anemia (hemoglobin < 12 g/dL) was examined in normal-weight Japanese women.

Methods: Serum adiponectin and blood hemoglobin were measured in 311 young women aged 18 - 24 years (A), 148 of their middle-aged mothers aged 39 - 60 years (B) and 322 community-dwelling women aged ≥ 65 years (C) with a mean body mass index (BMI) of 20.

Higher circulating adiponectin and lower orosomucoid were associated with postload glucose ≤70 mg/dL, a possible inverse marker for dysglycemia, in young Japanese women.

Objective: To examine whether serum adiponectin and orosomucoid were associated with postload glucose ≤70 mg/dL during an oral glucose tolerance test (OGTT), termed as postload low glycemia, a possible inverse marker for dysglycemia.

Research Design And Methods: 75 g OGTTs were performed with multiple postload glucose and insulin measurements over a 30-120 min period in 168 normal-weight Japanese women (18-24 years). Insulin resistance (IR) and β-cell function inferred from serum insulin kinetics during OGTT, fat mass and distribution by dual-energy X-ray absorptiometry (DXA), serum adiponectin and inflammatory markers were compared cross-sectionally between 39 women with and 129 women without postload low glycemia.

Higher Fasting and Postprandial Free Fatty Acid Levels Are Associated With Higher Muscle Insulin Resistance and Lower Insulin Secretion in Young Non-Obese Women.

Background: To assess the relationship of the shape of glucose concentration curve during a standardized meal test to serum free fatty acid (FFA) concentrations, insulin resistance and insulin secretion in young non-obese women.

Methods: Thirty-five young women had a standardized meal for breakfast with measurement of glucose, insulin and FFA concentrations at 0 (fasting), 30, 60 and 120 min; the areas under the concentration curves were calculated (AUCg, AUCi and AUCffa, respectively). Meal-induced insulin response (MIR) was calculated as the ratio between the incremental insulin and glucose concentrations during the first 30 min of meal tests.

Elevated serum adiponectin and tumor necrosis factor-α and decreased transthyretin in Japanese elderly women with low grip strength and preserved muscle mass and insulin sensitivity.

Objective: To determine if adiponectin levels are associated with low grip strength among the elderly independently of insulin resistance and inflammation.

Research Design And Methods: Cross-sectional associations were analyzed by logistic regression between low grip strength and body composition, elevated serum adiponectin (≥20 mg/L), and biomarkers of nutritious stasis, insulin resistance and inflammation in 179 community-living Japanese women. Sarcopenia was evaluated using the Asian criteria.

Association of serum orosomucoid with 30-min plasma glucose and glucose excursion during oral glucose tolerance tests in non-obese young Japanese women.

Objective: Inflammatory markers are elevated in insulin resistance (IR) and diabetes. We tested whether serum orosomucoid (ORM) is associated with postload glucose, β-cell dysfunction and IR inferred from plasma insulin kinetics during a 75 g oral glucose tolerance test (OGTT).

Research Design And Methods: 75 g OGTTs were performed with multiple postload glucose and insulin measurements over a 30-120 min period in 168 non-obese Japanese women (aged 18-24 years).

Appendicular muscle mass and fasting triglycerides predict serum liver aminotransferases in young female collegiate athletes.

Objective: We test the hypothesis that aspartate aminotransferase (AST) may be associated inversely with serum triglycerides (TG) and positively with high density lipoprotein (HDL) cholesterol in young athletes because athletes have larger amounts of muscle mass.

Research Design And Methods: Pearson's correlation coefficients were calculated between serum AST and alanine aminotransferase (ALT) and body composition identified by dual-energy X-ray absorptiometry, markers of insulin resistance, serum lipids, lipoproteins, apolipoproteins, adiponectin and leptin in 174 female collegiate athletes (18-22 years). Multivariate linear regression analyses were used to identify independent determinants of the aminotransferases.

The Cluster of Abnormalities Related to Metabolic Syndrome Is Associated With Reduced Glomerular Filtration Rate and Raised Albuminuria in Patients With Type 2 Diabetes Mellitus.

Background: As association of metabolic syndrome (MS) with chronic kidney disease (CKD) has not been extensively studied in patients with type 2 diabetes, we addressed these issues.

Methods: Intrapersonal means of 12 measurements of waist circumference, blood pressure and high-density lipoprotein (HDL) cholesterol and those of six measurements of fasting triglycerides during 12 months were calculated in a cohort of 168 previously reported Japanese patients with type 2 diabetes. Based on these means, MS was diagnosed according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria with the Asian definition of abdominal obesity.