Proteasome dysfunction mediates obesity-induced endoplasmic reticulum stress and insulin resistance in the liver.

Chronic endoplasmic reticulum (ER) stress is a major contributor to obesity-induced insulin resistance in the liver. However, the molecular link between obesity and ER stress remains to be identified. Proteasomes are important multicatalytic enzyme complexes that degrade misfolded and oxidized proteins.

Perceived parental rejection mediates the influence of serotonin transporter gene (5-HTTLPR) polymorphisms on impulsivity in Japanese adults.

This study examined (1) the interrelationships among 5-HTTLPR genotype, perceived parental rejection, and impulsivity, and (2) meditational models in which perceived paternal/maternal rejection mediates the relationship between the 5-HTTLPR genotype and impulsive behaviour. Participants included 403 adults (152 males and 252 females, mean age = 24.20) who provided genetic data and a set of the questionnaires (BIS11; Barratt Impulsiveness Scale-11 and EMBU; Egna Minnen av Bätraffande Uppfostran).

Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis.

Background: Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes. We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model.

Methodology/principal Findings: Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient plus high fat (MCD+HF) diet with or without 0.

Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus.

Background: The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver injury and the characteristics of nonalcoholic fatty liver disease (NAFLD) in DM patients.

Methods: In total, 5,642 DM patients and 365 histologically proven NAFLD patients were enrolled.

Fatty liver as a consequence and cause of insulin resistance: lessons from type 2 diabetic liver.

Obesity is less common in the Asian population, but Asian people may be susceptible to obesity-associated metabolic dysregulation. Accumulating evidence suggests that insulin resistance is closely associated with ectopic fat accumulation in the liver. Whether this correlation is due to a causal relationship between the conditions has long been the subject of debate.

Intra-aortic balloon pump induced dynamic left ventricular outflow tract obstruction and cardiogenic shock after very late stent thrombosis in the left anterior descending coronary artery.

An 81-year-old woman had undergone percutaneus coronary intervention to mid left anterior descending coronary artery with a drug-eluting stent for effort angina pectoris. Although she had remained asymptomatic for 3 years, she developed cardiogenic shock following acute myocardial infarction due to stent thrombosis. Her condition deteriorated despite successful revascularization and an initiation of intra-aortic balloon pump (IABP).

Impact of renal insufficiency on long-term clinical outcome in patients with heart failure treated by cardiac resynchronization therapy.

Background: Renal insufficiency is recognized as a predictor of mortality and adverse outcome in heart failure (HF) patients. However, the long-term clinical outcome of cardiac resynchronization therapy (CRT) in Japanese HF patients with renal insufficiency remains uncertain.

Methods: We evaluated 67 consecutive patients who underwent CRT at our hospital.

Biosensing based on magnetically induced self-assembly of particles in magnetic colloids.

Superparamagnetic beads and nonmagnetic beads of different sizes were assembled to form a "ring-structure" in a magnetorheological (MR) fluid solution by the application of external magnetic fields. For superparamagnetic beads and non-magnetic beads functionalized with probe and target molecules, respectively, the ring-structure was maintained even after removing the external magnetic field due to biomolecular bonding. Several experiments are described, including the formation process of ring-structures with and without molecular interactions, the accelerating effect of external magnetic fields, and the effect of biotin concentration on the structures of the rings.

Genetic polymorphisms of the human PNPLA3 gene are strongly associated with severity of non-alcoholic fatty liver disease in Japanese.

Background: Nonalcoholic fatty liver disease (NAFLD) includes a broad range of liver pathologies from simple steatosis to cirrhosis and fibrosis, in which a subtype accompanying hepatocyte degeneration and fibrosis is classified as nonalcoholic steatohepatitis (NASH). NASH accounts for approximately 10-30% of NAFLD and causes a higher frequency of liver-related death, and its progression of NASH has been considered to be complex involving multiple genetic factors interacting with the environment and lifestyle.

Principal Findings: To identify genetic factors related to NAFLD in the Japanese, we performed a genome-wide association study recruiting 529 histologically diagnosed NAFLD patients and 932 population controls.

Duodenal adenocarcinoma with neuroendocrine features in a patient with acromegaly and thyroid papillary adenocarcinoma: a unique combination of endocrine neoplasia.

A 67-year-old woman with familial clustering of thyroid papillary adenocarcinoma was diagnosed with acromegaly due to pituitary macroadenoma. She had multiple skin vegetations, but had no parathyroid and pancreas diseases. Before transsphenoidal surgery, she was further diagnosed as having a duodenal tumor and multiple hypervascular liver nodules.

Pharmacokinetics and pharmacodynamics of insulin aspart in patients with type 2 diabetes: assessment using a meal tolerance test under clinical conditions.

1. Few studies have evaluated the pharmacokinetics of rapid-acting insulin analogues in patients with Type 2 diabetes, especially under clinical conditions. The aim of the present study was to assess both the pharmacokinetics and pharmacodynamics of insulin aspart in Type 2 diabetic patients who were being treated with the analogue alone.

Postoperative diabetes insipidus associated with pituitary apoplexy during pregnancy.

Background: Pituitary apoplexy during pregnancy is so rare that only 15 cases (12 pituitary adenomas, 2 lymphocytic neurohypophysitis, and 1 normal pituitary gland) have been published to date. Here, we report the case of a pregnant woman presenting with pituitary apoplexy from a nonfunctioning pituitary adenoma and provide a possible mechanism and management option for postoperative diabetes insipidus (DI).

Case Presentation: A 26-year-old woman presented with sudden onset of headache and bitemporal hemianopsia in the 26th week of her first pregnancy.

Self-reported speed of eating and 7-year risk of type 2 diabetes mellitus in middle-aged Japanese men.

Objective: This cohort study investigated the association between eating speed and the incidence of type 2 diabetes in middle-aged Japanese men.

Materials/methods: Participants were 2,050 male employees of a metal products factory in Japan. We measured self-reported categorical eating speed.

Beneficial effect of branched-chain amino acid supplementation on glycemic control in chronic hepatitis C patients with insulin resistance: implications for type 2 diabetes.

Branched-chain amino acids (BCAAs) improve disorders of albumin metabolism, quality of life, subjective symptoms, and prognosis in patients with chronic hepatitis. However, it remains unclear whether they improve insulin resistance. We examined the effects of BCAAs on glucose tolerance and insulin sensitivity in patients with chronic hepatitis C and insulin resistance.

Inverse correlation between serum levels of selenoprotein P and adiponectin in patients with type 2 diabetes.

Background: We recently identified selenoprotein P (SeP) as a liver-derived secretory protein that causes insulin resistance in the liver and skeletal muscle; however, it is unknown whether and, if so, how SeP acts on adipose tissue. The present study tested the hypothesis that SeP is related to hypoadiponectinemia in patients with type 2 diabetes.

Methodology/principal Findings: We compared serum levels of SeP with those of adiponectin and other clinical parameters in 36 patients with type 2 diabetes.

CCR5 plays a critical role in obesity-induced adipose tissue inflammation and insulin resistance by regulating both macrophage recruitment and M1/M2 status.

C-C motif chemokine receptor (CCR)2 and its ligand, monocyte chemoattractant protein (MCP)-1, are pivotal for adipose tissue macrophage (ATM) recruitment and the development of insulin resistance. However, other chemokine systems also may play a role in these processes. In this study, we investigated the role of CCR5 in obesity-induced adipose tissue inflammation and insulin resistance.

[Novel strategies that target hepatokines for treatment of type 2 diabetes].

The liver may maintain systemic homeostasis by releasing secretory proteins into the blood stream. In fact, comprehensive gene expression analysis revealed that the liver in humans expresses various kinds of genes encoding secretory proteins. Recently, function-unknown liver-derived secretory proteins have been termed as hepatokines.

Identification of blood biomarkers of aging by transcript profiling of whole blood.

Immunological changes that inevitably occur with aging are related to the onset of various diseases including autoimmune diseases, immunodeficiency, as well as other age-reflecting (AR) diseases. They are becoming serious problems in the global trend of longevity. To understand the AR changes, we searched for genes whose expression profiles in the whole peripheral blood change dramatically as a function of age using the Agilent whole human genome 44K microarray.

Slowly progressive insulin-dependent diabetes in a patient with primary biliary cirrhosis with portal hypertension-type progression.

A 73-year-old woman had previously been diagnosed with CREST syndrome, PBC and diabetes. Hepatic fibrosis was not evident, in spite of the transudative ascites and active esophageal varices. ACA were positive, whereas AMA and anti-gp210 antibodies were negative.

Concentration-dependent dual effects of hydrogen peroxide on insulin signal transduction in H4IIEC hepatocytes.

Background: Oxidative stress induced by the accumulation of reactive oxygen species (ROS) has a causal role in the development of insulin resistance, whereas ROS themselves function as intracellular second messengers that promote insulin signal transduction. ROS can act both positively and negatively on insulin signaling, but the molecular mechanisms controlling these dual actions of ROS are not fully understood.

Methodology/principal Findings: Here, we directly treated H4IIEC hepatocytes with hydrogen peroxide (H2O2), a representative membrane-permeable oxidant and the most abundant ROS in cells, to identify the key factors determining whether ROS impair or enhance intracellular insulin signaling.

[Analysis of brain activity during delayed matching-to-sample test].

Despite recent advances in uncovering the neural signature of memory processing in humans, spatiotemporal characteristics of cerebral activity during mental transformation of the visual (color) memory to the visuo-spatial memory has not been studied. The aim of this study was to investigate the electrophysiological correlates of internal memory transformation based on the event-related potential analysis using a root mean square (RMS) and a standardized low resolution electromagnetic tomography (sLORETA). Eleven healthy human subjects completed a modified delayed matching-to-sample test in which the visual(color) short-term memory had to be transformed into the visuo-spatial memory according to the matching probe.

Association between coefficients of variation of the R-R intervals on electrocardiograms and post-challenge hyperglycemia in patients with newly diagnosed type 2 diabetes.

The aim of the present study was to examine whether there is a relationship between autonomic function and post-challenge hyperglycemia in patients with type 2 diabetes. Subjects included 122 Japanese patients newly diagnosed with type 2 diabetes. Autonomic nerve function was assessed using coefficients of variation of the R-R intervals on electrocardiograms (CVRR).

Dietary glycemic index and risk of type 2 diabetes mellitus in middle-aged Japanese men.

This cohort study investigated the association between dietary glycemic index (GI), glycemic load (GL), and the incidence of type 2 diabetes mellitus in middle-aged Japanese men, and the effect of insulin resistance and pancreatic B-cell function on the association. Participants were 1995 male employees of a metal products factory in Japan. Dietary GI and GL were assessed using a self-administered diet history questionnaire.