Yuji Tajiri

Kurume University · Division of Endocrinology and Metabolism

Background: Obesity and type 2 diabetes mellitus (T2DM) are often accompanied with a disrupted diurnal rhythm of eating and sustained anabolic state, leading to metabolic inflexibility. In the present study, we plan to investigate effects of a sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin (CANA), on such a metabolic inflexibility...

Background Obesity and type 2 diabetes mellitus (T2DM) are often accompanied with a disrupted diurnal rhythm of eating and sustained anabolic state, leading to metabolic inflexibility. In the present study, we plan to investigate effects of a sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin (CANA), on such a metabolic inflexibility,...

AimTo investigate long-term effects of sodium-glucose co-transporter 2 inhibitor (SGLT2i) on anthropometric and metabolic factors in Japanese patients with type 2 diabetes (T2DM).Patients and Methods This is a retrospective observation study. Forty-six outpatients with T2DM (32 men and 14 women, 51 ± 13 years old, BMI 27.9 ± 4.8, means ± S.D.) who...

Objective Although a number of studies have shown that both short and long sleep durations were associated with the risk of metabolic disorders related to obesity, the underlying mechanism is still not fully understood. In this study, we analyzed the association of sleep duration with metabolic, anthropometric, and lifestyle factors in patients wit...

Background and Aims: It is currently unclear whether sodium–glucose co-transporter 2 (SGLT2) inhibitor administration can improve the insulin sensitivity as well as rapidly reduce plasma glucose concentrations in humans during the early phase of treatment initiation. This study aimed to investigate the effect of SGLT2 inhibitor on insulin sensitivi...

A 22-year-old Japanese woman consulted an endocrinologist due to persistent galactorrhea for the past 10 months. She had hyperprolacinemia and had previously been diagnosed with type 2 diabetes mellitus based on her glycohemoglobin level of 11.6%. After two months, she was admitted to our hospital and finally diagnosed with prolactinoma. For the tr...

Patient: Female, 40 Final Diagnosis: Autoimmune polyendocrine syndrome type 3 Symptoms: Thirst • polyuria • weight-loss Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective Rare co-existance of disease or pathology Background Patients with type 1 diabetes mellitus, myasthenia gravis (MG), and Hashimoto disease are...

We previously reported that voluntary exercise contributed to the amelioration of abnormal feeding behavior with a concomitant restoration of ghrelin production in a rat model of obesity, suggesting a possible relationship between exercise and appetite regulating hormones. Ghrelin is known to be involved in the brain reward circuits via dopamine ne...

Most childhood cancer survivors who undergo hematopoietic stem cell transplantation subsequently develop impaired glucose tolerance and hypertriglyceridemia. These conditions are presumably associated with total body irradiation-related acquired lipodystrophy and may lead to cardiovascular disease. Metreleptin (recombinant leptin) may help in impro...

Although accumulating evidence has shown that there is a U-shaped association between sleep duration and the risk of metabolic disorders related to obesity, its underlying mechanism is still not fully understood. In this study, we analyzed the association of sleep duration with metabolic, anthropometric, and lifestyle factors in patients with type...

Aims/Introduction: Several lines of evidence suggest that dysregulation of the WNT signaling pathway is involved in the pathogenesis of type 2 diabetes. This study was performed to elucidate the effects of a high-fat/high-sucrose (HF/HS) diet on pancreatic islet functions in relation to modulation of WNT ligand expression in β-cells. Materials and...

Many studies have reported the effect of SGLT2 inhibition on body composition. However, its effect on water distribution and the resultant influence on body composition measures are still unclear. The subjects of this study consisted of 29 tofogliflozin (TOFO) -treated type 2 diabetic inpatients aged 48±14 years with BMI of 29.4±6.3 kg/m2, and 29 a...

Aims/Hypothesis The aim of this study was to elucidate the mechanism by which severe hypoglycemia accelerates vascular complications. Furthermore, we assessed the possible protective effect of ketone bodies against the endothelial cell damage caused by glucose deficiency. Methods Human umbilical vein endothelial cells (HUVECs) were cultured at a g...

Objective Type 2 diabetes is a progressive disease characterized by insulin resistance and insulin secretory dysfunction. In this study, we assessed the factors contributing to an insulin secretory defect in type 2 diabetes patients. Methods The subjects consisted of 382 patients with type 2 diabetes, aged 57±13 years. We estimated the β-cell funct...

In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague-Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) wi...

Aims/IntroductionTo assess the effects of SGLT2 inhibitor therapy on the pathophysiology of type 2 diabetes.Materials and Methods We administered ipragliflozin to 21 inpatients with type 2 diabetes for 7 days, and analyzed the diurnal profiles of plasma glucose and 3-hydroxybutyrate (3HB). Twenty-one age-, sex-, and BMI-matched diabetic patients se...

Aim To examine the effects of supplementing aspirin therapy with folic acid on vascular endothelial function among patients with type 2 diabetes. Methods This was a randomized open label crossover study. Fifteen patients with type 2 diabetes (group A) were first treated with 100 mg/day aspirin plus 20 mg/day folic acid for 1 week and then received...

To assess the significance of ketogenesis in the management of diabetes mellitus, we analyzed the factors associated with the diurnal variation of the plasma ketone body levels. The subjects consisted of 220 patients with type 2 diabetes, aged 60 ± 15 years, without advanced complications. They ate a standardized, low-fat meal at 8:00, 12:00, and 1...

Patient empowerment has recently been proposed as an important concept in self-management for effective glycemic control. A concise self-completed questionnaire for patients with type 2 diabetes mellitus was created to comprehensively evaluate their empowerment on the basis of self-managed dietary/exercise behaviors, psychological impact, and famil...

Aims. Efficacy and safety of DPP-4 inhibitor, sitagliptin, add-on therapy to insulin were investigated in Japanese patients with type 2 diabetes. Subjects and Methods. Two hundred and sixteen patients (126 men, 65 ± 12 years old, BMI 24.9 ± 4.5, means ± S.D.) who had been treated by insulin alone or insulin combined with other oral hypoglycemic age...

The purpose of this study was to assess the efficacy of insulin degludec compared with insulin glargine and to find a safer way of switching from insulin glargine to insulin degludec. By use of a crossover design we compared preprandial blood glucose levels for patients with type 1 diabetes when insulin glargine or insulin degludec was injected in...

Background: The enzyme ghrelin O-acyltransferase (GOAT) catalyzes the acylation of ghrelin. The molecular form of GOAT, together with its reaction in vitro, has been reported previously. However, the subcellular processes governing the acylation of ghrelin remain to be elucidated. Methods: Double immunoelectron microscopy was used to examine change...

Adiponectin-transgenic mice had many small adipocytes in both subcutaneous and visceral adipose tissues, and showed higher sensitivity to insulin, longer life span, and reduced chronic inflammation. We hypothesized that adiponectin regulates Wnt signaling in adipocytes and thereby modulates adipocyte proliferation and chronic inflammation in adipos...

Nighttime food intake is associated with weight gain and higher HbA1c levels. We experienced night eaters who have no memory of their nocturnal eating in the morning. In this study, the curious night eating behavior was designated as "unremembered nocturnal eating syndrome (UNES)". We screened 1,169 patients with diabetes for sleep quality and abno...

To assess the effect of adiponectin on the circadian rhythm disturbances associated with metabolic syndrome, we generated a KK/Ta mouse line expressing the human adiponectin transgene in the liver. Locomotor activity of control C57BL/6 mice was highest during the beginning of the dark period and low during the light period. Under constant darkness,...

Aims: An appropriate questionnaire for assessing family support of self-management behavior of Japanese Type 2 diabetes patients has yet to be developed. We produced a Japanese version of the Diabetes Family Behavior Checklist (DFBC) and tested its reliability and validity. Methods: The study enrolled Japanese patients with Type 2 diabetes melli...

We compared the effects of exercise alone and in combination with a calcium channel blocker (amlodipine) or an angiotensin receptor blocker (valsartan) in hypertensive patients. Our results indicated that exercise therapy exerted similar effects on systolic blood pressure whether administered alone or in combination with amlodipine or valsartan; ho...

A-type (atrial) natriuretic peptide (ANP) levels in the heart and plasma were examined by immunohistochemistry, electron microscopy, and radioimmunoassay (RIA) in angiotensin II type 1a receptor knockout (Agtr1a KO) mice. Additionally, the ANP mRNA level in the heart was measured using a real-time polymerase chain reaction (PCR) assay. The blood pr...

Ghrelin is an acylated peptide hormone mainly secreted from the stomach. When administrated externally it modulates vascular tone mainly through the regulation of autonomic nerve activity. However, the effects of blood pressure (BP) on the production and secretion of ghrelin remain to be clarified. We examined the stomach and plasma levels of ghrel...

Thigh subcutaneous fat has recently been advocated to have a favorable association with insulin resistance or cardiovascular disease (CVD) risk, in contrast to abdominal and visceral fat. However, because individual regional fat components are strongly correlated with each other, multiple regression analysis of these independent variables in the sa...

We previously reported that transgenic (Tg) expression of adiponectin significantly prolonged the lifespan of normal mice. The aim of this study was to elucidate the mechanism involved in the longevity effects of adiponectin using KK/Ta mice, a murine model of metabolic syndrome. We established a Tg line of KK/Ta (Tg-KK/Ta) mice expressing human ad...

We studied the efficacy of sitagliptin in type 2 diabetic patients of our outpatient clinics. Since December in 2009, 164 patients have been treated by sitagliptin for their management of diabetes. HbA1c decreased by 0.8% in all patients without any change in mean body weight after 3 months. However, actually HbA1c did not decrease in 30 patients,...

Atrial (A-type) natriuretic peptide (ANP) is vasodilative hormone involved in the regulation of blood pressure and volume homeostasis. In this study, we examined the differences of the auricular and plasma ANP distribution by immunohistochemistry, ultrastructural morphometry, and radioimmunoassay in five strains of mice. The ANP-immunoreactivities...

An abnormal eating behavior is often associated with diabetes mellitus in individuals. In the present study, we investigated the mechanisms underlying the relationship among uncontrolled diabetes, food intake, and the production of ghrelin, an orexigenic hormone, in spontaneous diabetic Torii (SDT) rats. Male SDT rats and age-matched control Spragu...

The metabolic clearance rate (MCR) of glucose has been defined as the value of the glucose infusion rate (GIR) divided by the glucose concentration and could be thus expected to be a robust marker at various glucose concentrations. We evaluated the validity of MCR compared with GIR in 15 healthy subjects and 38 type 2 diabetes patients. The glucose...

Besides n-octanoyl ghrelin (O-ghrelin), there is another acyl-form of ghrelin; n-decanoyl ghrelin (D-ghrelin), which has a decanoic acid modification. In this study, we examined the kinetics of D-ghrelin immunoreactivity in human plasma in comparison to O-ghrelin or total ghrelin by using a D-ghrelin-specific radioimmunoassay. The dynamics of plasm...

Aim: The aim of this study was to assess the classification and clinical characteristics of interferon (IFN)-related diabetes. Methods: Cases with IFN-related diabetes in Japan were retrieved through web search engines for medical literature until July in 2009, and unreported data were obtained from the authors by letter or e-mail. Results: We...

We compared blood glucose profile when glargine or detemir was injected once daily before dinner in combination with pre-meal insulin lispro by a crossover design. Glargine showed lower post-dinner and bedtime glucose levels in Type 1 diabetes, and lower pre-dinner and post-dinner glucose levels in Type 2 diabetes than detemir.

Introduction: The aim of the present study is to propose a novel index of insulin sensitivity instead of homeostasis model assessment of insulin resistance (HOMA‐IR), which has a fundamental limitation of validity when applied to subjects with lower insulin secretions or high fasting plasma glucose (FPG) levels. Materials and Methods: A total of 25...

Sunitinib is a multi-targeted tyrosine kinase inhibitor that is effective for advanced renal cell carcinoma. However, sunitinib often causes hypothyroidism. In this study, we report eight cases with thyroid dysfunction that occurred during sunitinib treatment for advanced renal cell carcinoma. In seven cases, mild hypothyroidism developed early in...

Sir, Although the validity of glycoalbumin (GA) instead of haemoglobin A1c (HbA1c) measurement in patients on haemodialysis (HD) has recently been discussed by some investigators [1,2], an appropriate indicator for glycaemic control in patients with pre-dialysis chronic renal failure (CRF) has only rarely been reported [1]. The application of eryt...

The aim of the present study was to evaluate characteristics of body composition in Japanese patients with type 2 diabetes. Measurement of regional body composition was performed using bioelectrical impedance analysis (INBODY720) in 198 patients with type 2 diabetes (group D) and 198 apparently healthy subjects matched for age, gender, and body mas...

The aim of this study was to evaluate the variation of fasting serum C-peptide (S-CPR) levels, as a marker for endogenous insulin secretion after admission in Japanese patients with type 2 diabetes mellitus (T2DM). S-CPR levels together with other metabolic factors were measured in 234 T2DM patients twice: at the beginning and at the end of admissi...

The aim of the study is to identify the clinical characteristics of Japanese patients with young-onset type 2 diabetes (YT2D). Family history of diabetes and clinical data were collected for 30 unrelated males (from 11 to 20 years old at age of onset) and 20 females (from 10 to 20 years old at age of onset) with YT2D diagnosed at ≤ 20 years of age....

Waist circumference (WC) was measured in 200 Japanese patients with type 2 diabetes mellitus (T2DM: male 106, female 94, mean age 61 years old) who had been admitted in our hospital, and relationship with various risk factors to predict future cardiovascular disease (CVD) was analyzed. There was a positive and statistically significant trend in WC...

The aim of this study is to explore appropriate indicators for the efficacy of pioglitazone (Pio) before and during treatment of Japanese patients with type 2 diabetes mellitus (T2DM). Forty-eight Japanese patients with T2DM (22 men, 26 women, 60 +/- 2 years old) were enrolled and treated with 15 mg/day of Pio for 12 weeks. Before and after the tre...

To assess the relationship between high-sensitivity (HS) C-reactive protein (CRP) and metabolic syndrome (MetS) or atherosclerosis and to assess effects of strict metabolic control on the degree of inflammation and MetS in patients with type 2 diabetes. Four hundred thirteen patients with diabetes were enrolled in the cross-sectional study. Of thes...

The mechanism for beta-cell dysfunction induced by glucosamine has not yet fully been investigated previously. To investigate the effects of glucosamine on insulin release or gene expression related to glucose metabolism in rat islets cultured with glucosamine for 24 hours. After islets were cultured with glucosamine or diazoxide, we measured gluco...

Biotin (vitamin H) plays an important role as a cofactor in glucose or lipid metabolism. We showed that biotin potentiated glucose-induced insulin release in isolated rat islets, while biotin alone did not affect insulin release. Coculture with biotin in islets for 48 hours significantly enhanced glucose-induced insulin release or islet insulin con...

A 51-year-old man diagnosed with Cowden disease based on multiple facial trichilemmoma, oral mucosal papillomatosis, palmo-planter keratosis and muliple hamartomatous polyps in the gastrointestinal tract had had a heterozygous flameshift mutation identified in his PTEN gene (4 base insertion after codon 221), believed to be responsible for the dise...

Bezafibrate is an activator of peroxisome proliferator-activated receptors (PPAR) α. The present study was performed to investigate the effects of bezafibrate and the PPAR α activator, 4-Cholro-6-(2.3-xylidino)-2-pyrimidin-ylthio acetic acid (WY14643), on the β-cell function of rat pancreatic islets in vitro. In islets cultured with 300 μM bezafibr...

Adenosine-3',5'-cyclic monophosphate (cyclic AMP) promotes exocytosis of insulin in pancreatic beta cells. This study was performed to investigate the role of cyclic AMP in the pathogenesis of glucose desensitization in rat pancreatic islets. In islets cultured with high glucose for 48 hours, 27 mmol/L glucose-induced insulin release was markedly i...

It is well known that acute administration of fatty acids enhances insulin release from beta cells, although chronic exposure to fatty acids inhibits insulin release (lipotoxicity). The mechanism for these reciprocal effects of fatty acids on insulin release remains to be elucidated. The present study was performed to investigate the effects of fat...

We investigated the effects of aminoguanidine (AG) on β-cell functions in an insulin secreting cell line (INS-1). Culture with 27 mM glucose for one week markedly decreased both insulin release and insulin content compared to culture in 0.8 mM or 3.3 mM glucose. Relative to culture at 27 mM glucose alone, the co-exposure to 1 mM AG almost doubled b...

Hyperglycemia exerts negative effects on B-cell functions that may involve oxidative stress. This was tested for by investigating effects of D-alpha-tocopherol (vitamin E), known as a free radical scavenger, on B-cell functions. For in vivo testing, rat pancreatic islets were transplanted syngeneically under the kidney capsule in streptozotocin-ind...

Chronic hyperglycemia has adverse effects on B cell function. We investigated the possible role of advanced glycosylation end products (AGEs) in glucotoxicity. Rat islets were cultured at different glucose concentrations for 1-6 weeks in RPMI 1640. Culture was performed with or without aminoguanidine (AG), which is known to prevent AGE formation in...

The present study was undertaken to evaluate the effects of a selective thromboxane synthetase inhibitor (OKY-046) on urinary prostaglandins (PGs) excretion and renal parameters such as endogenous creatinine clearance rate (Ccr) and urinary protein excretion in streptozotocin (STZ)-induced diabetic rats. STZ-diabetic rats were divided into two grou...

In 43 patients with non-insulin dependent diabetes mellitus (NIDDM) associated with hypercholesterolemia, the effect of pravastatin, a potent HMG CoA-reductase inhibitor, on serum lipids, apolipoproteins and lipoprotein (a) was examined. After 1 to 3 months administration of 10 mg per day of pravastatin, the serum levels of total cholesterol, trigl...

We evaluated the effects of thromboxane synthetase inhibitor, OKY-046, on urinary albumin and prostaglandin (PG) excretion in 14 patients with non-insulin-dependent diabetes mellitus (NIDDM). Urinary excretion of 6-keto-PGF1 alpha (a stable metabolite of PGI2), TXB2 (a stable metabolite of TXA2) and PGE2 in NIDDM patients was comparable with that i...

Recently the beneficial effects of captopril (angiotensin-converting-enzyme inhibitor) on diabetic nephropathy, especially proteinuria, have been reported by some investigators. The mechanism whereby proteinuria is reduced, however, have not been clarified yet. The present study was undertaken to evaluate the effects of captopril on urinary albumin...

The effect of galanin on pancreatic hormone release was studied using isolated perifused rat pancreatic islets. In the presence of 100 mg/dl glucose, 10(-8) mol/L galanin significantly inhibited the basal somatostatin release compared with the perifusion without galanin, whereas there was no significant change in the basal insulin and glucagon rele...

The albumin index (mg/g . creatinine) was determined in untimed spot urine collected in the early morning from 92 randomly selected outpatients with noninsulin-dependent diabetes mellitus (NIDDM). The patients were divided into three groups: 49 patients with normo-albuminuria (albumin index less than 9.1), 24 with micro-albuminuria (albumin index b...

Vibratory perception threshold (VPT) in diabetic patients (NIDDM) with (n=13) or without neuropathy (n=12) and age matched control subjects (n=12) was measured at the right internal malleolus using a vibratory perception meter (TM-31A). After continuous vibratory stimulation at 150μm amplitude for 5 min, VPT was again measured at 0, 2 and 5min. VPT...

Measurement of serum fructosamine (FRA) by means of a Roche kit is a simple and reliable method for estimating glycosylated serum proteins. The level of FRA can be affected by hyperglycemia in diabetics and an abnormal metabolic state of serum proteins such as albumin in patients with renal failure, liver cirrhosis, and thyroid dysfunction. We meas...