Takashi Nomiyama

Fukuoka University · Endocrinology and Diabetes Mellitus

The Aging Males' Symptoms (AMS) score, developed to screen for late-onset hypogonadism (LOH), contains 17 questions regarding mental, physical, and sexual parameters. In the Japanese guidelines, a free testosterone (FT) <8.5 pg/mL is recommended for testosterone treatment. However, previous studies have shown no correlation between total AMS scores...

Purpose: The effects of two types of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal function remain unclear. Thus, we investigated the effect of anagliptin (ANA) and sitagliptin (SITA) on renal function in patients with type 2 diabetes who participated in the randomized evaluation of ANA versus SITA on low-density lipoprotein-cholesterol (LDL-...

Cancer is a major cause of death in patients with diabetes. Incretin therapy has received much attention because of its tissue-protective effects. We have previously reported an anti-breast cancer effect of glucagon-like peptide-1 receptor agonist exendin-4 (Ex-4). An anti-cancer effect of metformin is well recognized. Therefore, we examined the ef...

Cancer is a major cause of death in patients with type 2 diabetes mellitus (T2DM) and lung cancer is one of the most prevalent cancers in patients with T2DM. In the present study, we examined the anti-cancer effect of the Sodium-glucose cotransporter 2 (SGLT2) inhibitor, canagliflozin, using a lung cancer model. In lung cancer tissues from non-T2DM...

Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Treatment with a statin leads to a compensatory increase in circulating PCSK9 level. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to decrease LDL cholesterol (L...

Purpose: Experimental evidence has suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors have an anti-inflammatory effect as well as a glucose-lowering effect, but this has yet to be confirmed in diabetic patients. Therefore, we examined the anti-inflammatory effects of two kinds of DPP-4 inhibitors in patients who participated in the randomize...

Recently, the prevention of cardiovascular events has become one of the most important aims of diabetes care. Peroxisome proliferator-activated receptor (PPAR) agonists have been reported to have vascular protective effects. Here, we examined whether pemafibrate, a selective PPAR alpha agonist, attenuated neointima formation after vascular injury a...

Objective: Among fatty acid-binding proteins (FABPs), secreted forms of FABP4 and FABP5, which are expressed in adipocytes and macrophages, act as bioactive molecules. We investigated concentrations of FABP4 and FABP5 in patients with type 2 diabetes mellitus. Methods: As a sub-analysis study of the Randomized Evaluation of Anagliptin vs. Sitaglipt...

Background: Fatty acid-binding protein 4 (FABP4) acts as a novel adipokine, and elevated FABP4 concentration is associated with obesity, insulin resistance and atherosclerosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a class of antidiabetic drugs, have distinct structures among the drugs, possibly leading to a drug class effect and each drug ef...

Low testosterone and hyperuricemia are associated with metabolic syndrome (MetS). However, little is known about the nature of the relationships between serum testosterone and sex hormone‐binding globulin (SHBG) concentrations, and hyperuricemia. We evaluated the relationships between serum testosterone (calculated bioavailable testosterone [cbT],...

Aims/introduction: Incretin therapy is a common treatment for type 2 diabetes mellitus. We have previously reported an anti-prostate cancer effect of glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4. The attenuation of cell proliferation in prostate cancer cell line was dependent on GLP-1R expression. Here, we examined the relationship...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are one of the most frequently prescribed anti-diabetic agents in Japan, and they are often used in combination with insulin secretagogues, such as sulfonylureas and glinides. In the present study, we determined the efficacy and safety of the use of repaglinide or glimepiride, a sulfonylurea, in combinati...

The effects of antidiabetic agents on lipoprotein subclasses are assumed to be pivotal, but this assumption has not been studied. We evaluated lipoprotein subclasses in patients, randomly selected from REASON (Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes) Trial participants, with type-2 d...

Cancer is currently one of the major causes of death in patients with type 2 diabetes mellitus. We previously reported the beneficial effects of the glucagon-like peptide-1 receptor agonist exendin-4 against prostate and breast cancer. In the present study, we examined the anti-cancer effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor i...

Background: Anagliptin, a dipeptidyl peptidase-4 inhibitor, is reported to reduce the level of low-density lipoprotein cholesterol (LDL-C). The underlying mechanism of this effect and effect on lipid metabolism however remains uncertain. Aim and methods: We therefore evaluate the effects of anagliptin on lipid metabolism-related markers compared...

Additional reductions in low-density lipoprotein-cholesterol (LDL-C) via antidiabetic therapies should be considered in statin-using patients with sub-optimal LDL-C levels. We compared the efficacy of anagliptin and sitagliptin, two antidiabetic therapies, in reducing LDL-C in type 2 diabetic patients. A randomized, open-label, parallel-group trial...

Cancer is a major cause of death in patients with diabetes. Incretin therapy has received much attention, because of its tissue protective effects beyond glycemic control. We have previously reported anti-prostate cancer effect of Ex-4 and metformin (Diabetes 2014, PLOS ONE 2015). In addition, we have recently reported that Ex-4 attenuates breast c...

Incretin therapy is one of the most popular treatment for type 2 diabetes. We have previously reported anti-prostate cancer effect of GLP-1R agonist Exendin-4(Ex-4) (Diabetes 2014, PLOS ONE 2015), and LEADER trial suggested that GLP-1R agonist could reduce prostate cancer. In our previous report, the attenuation of prostate cancer cell proliferatio...

Recently, the prevention of cardiovascular events has become one of most important purpose of diabetes care. We have previously reported that GLP-1 receptor agonist exendin-4 (BBRC 2011) and DPP-4 inhibitor linagliptin (Cardiovasc Diabetol 2014) attenuate neiontima formation after vascular injury. On the other hand, PPAR agonist is also reported it...

Low endogenous testosterone and sex hormone-binding globulin (SHBG) concentrations have been reported to be associated with metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). However, little is known about the relationships between testosterone or SHBG and liver fibrosis in NAFLD. Thus, we aimed to clarify the relationships be...

Incretin therapy has emerged as one of the most popular medications for type 2 diabetes. We have previously reported that the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin attenuates neointima formation after vascular injury in non-diabetic mice. In the present study, we examined whether combined treatment with linagliptin and the sodium glu...

Introduction: In an effort to develop a selective androgen receptor modulator (SARM) with beneficial activity in energy homeostasis, we previously screened 119 steroid analogs for the ability to induce uncoupling protein-1 (UCP-1) mRNA without increasing prostate-specific antigen promoter activity in human prostate cancer cell line, LNCap. As a res...

Orphan nuclear receptor NR5A1 (also called adrenal 4-binding protein/steroidogenic factor-1) is the major regulator of differentiation and function of the adrenal cortex. Adrenocortical carcinoma is rare and deadly with few therapeutic options and is known to have the tendency of increased NR5A1expression along with increased steroidogenesis. Most...

The recently discovered circular RNAs (circRNAs) are mostly formed by back-splicing where the downstream 5′ splice site splices to the upstream 3’ splice site by conventional pre-mRNA splicing. These circRNAs regulate gene expression by acting as sponges for micro-RNAs or RNA-binding proteins. Here we show that the NR5A1 (previously called Ad4BP or...

We previously identified a novel selective androgen receptor modulator, S42, that does not stimulate prostate growth but has a beneficial effect on lipid metabolism. S42 also increased muscle weight of the levator ani in orchiectomized Sprague–Dawley rats. These findings prompted us to investigate whether S42 has a direct effect on cultured C2C12 m...

Aims: Recently, incretin therapy has attracted increasing attention because of its potential use in tissue-protective therapy. Neuron-derived orphan receptor 1 (NOR1) is a nuclear orphan receptor that regulates vascular smooth muscle cell (VSMC) proliferation. In the present study, we investigated the vascular-protective effect of Exendin-4 (Ex-4)...

Objectives: The high-mobility group A protein 1a (HMGA1a) protein is known as a transcription factor that binds to DNA, but recent studies have shown it exerts novel functions through RNA-binding. We were prompted to decipher the mechanism of HMGA1a-induced alternative splicing of the estrogen receptor alpha (ERα) that we recently reported would al...

Sodium-glucose co-transporter-2 inhibitors are newly established anti-diabetic agents with a unique glucose-lowering mechanism. In the present study, we investigated the efficacy and safety of the sodium-glucose co-transporter-2 inhibitor ipragliflozin (Ipra) for metabolic markers and cardiovascular parameters in Japanese patients with type 2 diabe...

Pleiotropic benefits of incretin therapy beyond glycemic control have been reported and receiving much attention. Cancer is one of major causes of death in patients with type 2 diabetes. We have previously reported Exendin-4(Ex-4), a glucagon-like peptide-1 receptor agonist, attenuates prostate cancer growth by the inhibition of ERK-MAPK phosphoryl...

Currently, cancer is one of major cause of death in patients with type 2 diabetes. We have previously reported the anti-prostate and anti-breast cancer effect of GLP-1R agonist Exendin-4 (Diabetes 2014, Endocrinology 2017). In the present study, we examined the anti-cancer effect of SGLT2 inhibitor ipragliflozin (Ipra) using a breast cancer model....

Incretin therapy is one of the most popular treatment for type 2 diabetes. GLP-1R agonist has received much attention, because of its tissue protective effects beyond glycemic control. We have previously reported anti-prostate and anti-breast cancer effect of GLP-1R agonist Exendin-4(Ex-4) (Diabetes 2014, PLOS ONE 2015, Endocrinology 2017). In our...

Cancer is a major cause of death in patients with diabetes. Incretin therapy has received much attention, because of its tissue protective effects beyond glycemic control. We have previously reported anti-prostate cancer effect of Ex-4 and metformin (Diabetes 2014, PLOS ONE 2015). In addition, we have recently reported that Ex-4 attenuates breast c...

We previously identified a novel selective androgen receptor modulator (SARM), S42, which does not stimulate prostate growth but has a beneficial effect on lipid metabolism. In the prostate cancer (PC) cell line LNCaP, S42 did not induce androgen receptor (AR) transactivation but antagonized 5α-dihydrotestosterone (DHT)-induced AR activation. Next,...

Background Reduction of low-density lipoprotein cholesterol (LDL-C) is important for patients with a high risk for atherosclerotic events, such as patients with diabetes and other risk factors. Anagliptin was reported to reduce LDL-C for 12 weeks in phase III trials regardless of the use of statins, but it is uncertain whether this effect is common...

Incretin therapies have received significant attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients with diabetes mellitus. We previously reported anti-prostate cancer effects of the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist exe...

Background A high prevalence of cancers in metabolic disorders, like metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM), recently has been noted, including prostate cancer (PC), which is androgen‐sensitive. However, the pathological relationship among testosterone and insulin and insulin‐like growth factor (IGF)‐1 signaling in relation t...

An age-associated androgen decrease and its pathological conditions are defined as late-onset hypogonadism (LOH). Among the various symptoms associated with LOH, a visceral fat increase is strongly associated with relatively low levels of testosterone. However, few studies have investigated the relationship between the Aging Males' Symptoms (AMS) s...

A 37-year-old female patient was hospitalized because of general fatigue and loss of axillary and pubic hair after massive bleeding at delivery of her third child. The basal levels of both plasma adrenocorticotropin hormone (ACTH) and serum cortisol were very low, 5.2 pg/mL and 1.9 μg/dL, respectively. Based on the fact that ACTH showed a low respo...

Aryl hydrocarbon receptor interacting protein (AIP) is thought to be a tumor suppressor gene, as indicated by a mutational analysis of pituitary somatotroph adenomas. However, the physiological significance of AIP inactivation in somatotroph cells remains unclear. Using CRISPR/Cas9, we identified a GH3 cell clone (termed GH3-FTY) in which Aip was g...

Nucleotide sequence of Aip exon 4 and schematic structure of Aip protein. (A) Nucleotide sequence of normal (wild-type) and mutant Aip exon 4 in GH3-FTY cells. GH3-FTY cells contained heterozygous mutants of an adenine insertion at c.496 and a two base deletion at c.496-497, causing premature stop codons at codon 173 (TGA) and codon 172 (TGA), resp...

Primer list. Primers 1–6 were used to amplify Aip. Primers 7–13 were used for qPCR to determine the mRNA expression levels of respective genes. (PDF)

Antibody list. (PDF)

Introduction: In treatment algorithms of type-2 diabetes mellitus (T2DM) in Western countries, biguanides are recommended as first-line agents. In Japan, various oral hypoglycemic agents (OHAs) are available, but prescription patterns are unclear. Materials and methods: Data of 7,108 and 2,655 T2DM patients in study-1 and -2, respectively, were...

Introduction: Recent studies indicate that cancer is a new complication of diabetes. In Japan, cancer is the most critical cause of death in patients with type 2 diabetes. Areas covered: Unlike diabetic angiopathies, diabetes does not accelerate the onset and progression of cancer, even though diabetes and cancer exhibit very similar pathophysiolog...

A 38-year-old man diagnosed with craniopharyngioma at 8 years old underwent repeated surgery and radiation therapy. Complications included panhypopituitarism including growth hormone deficiency and hypogonadism at 13 years old. At 26 years of age, a slight fatty liver was found, which finally developed into liver cirrhosis (LC) at 35 years old. Vir...

Introduction Recently, the pleiotropic benefits of incretin-based therapy have been reported. We have previously reported that Exendin–4, a glucagon-like peptide–1 (GLP–1) receptor agonist, attenuates prostate cancer growth. Metformin is known for its anti-cancer effect. Here, we examined the anti-cancer effect of Exendin–4 and metformin using a pr...

Background: Some oral hypoglycemic agents (OHAs) have been suggested to reduce the risk of cardiovascular disease (CVD) in type-2 diabetes mellitus (T2DM). We ascertained if OHAs affect CVD risk in a cohort analysis of a multicenter medical-cost accounting database in Japan. Methods: Data of 4095 and 1273 T2DM patients in study 1 and study 2, re...

Background Incretin therapy is feasible in patients with type 2 diabetes mellitus undergoing hemodialysis (HD). However, few studies have examined the safety and efficacy of this therapeutic approach in patients with diabetes and renal impairment. Here, we examined glycemic control and the anti-oxidative-stress effects of the dipeptidyl peptidase (...

The biological actions of testosterone(T) and estrogens(E) are mediated via androgen receptor(AR) and estrogen receptor(ER), respectively. Testosterone also exerts its effect by conversion to estrogens by aromatase in peripheral tissues. Recently, from the detailed analysis of the phenotype of human or mouse mutant of AR, ER and aromatase, T-AR, E-...

The nuclear receptor NOR1 is an immediate-early response gene implicated in the transcriptional control of proliferation. Since the expression level of NOR1 is rapidly induced through cAMP response element binding (CREB) protein-dependent promoter activation, we investigated the contribution of histone acetylation to this transient induction. We de...

Background Recently, glucagon-like peptide-1 (GLP-1)-based therapy, including dipeptidyl peptidase-4 (DPP-4) inhibitors and GLP-1 receptor agonists, has emerged as one of the most popular anti-diabetic therapies. Furthermore, GLP-1-based therapy has attracted increased attention not only for its glucose-lowering ability, but also for its potential...

Endogenous testosterone is known to be protective against metabolic syndrome (MetS) in men. While various markers of testosterone status including serum total testosterone (TT), free testosterone (measured using analogue ligand RIA [aFT]), calculated FT (cFT), calculated bioavailable T (cbT), and sex-hormone binding globulin (SHBG) are recognized,...

The research to develop a drug, so called selective androgen receptor modulator (SARM) , which shows beneficial androgenic action on bone and muscle, but hardly possesses the stimulatory action on prostate has been making a progress. However, no drug is available in the market at present. Most of such drugs are developed, aiming at the application...

Recently, pleiotropic benefits of incretin therapy beyond glycemic control have been reported. Although cancer is one of the main causes of death in diabetic patients, few reports describe the anti-cancer effects of incretin. Here, we examined the effect of the incretin drug Exendin-4, a glucagon-like peptide-1 receptor (GLP-1R) agonist, on prostat...

The prevalence of primary aldosteronism (PA) is around 3-15% in patients with hypertension. Hypertension is a frequent complication of type 2 diabetes mellitus (DM) because of the close etiological relationship between these two diseases. However, the possibility of PA in patients with DM and hypertension is often overlooked and the prevalence of P...

Subclinical Cushing's syndrome (SCS) associated with adrenal incidentaloma is usually characterized by autonomous cortisol secretion without overt symptoms of Cushing's syndrome (CS). Although the diagnostic criteria for SCS differ among countries, the 1 mg dexamethasone suppression test (DST) is essential to confirm the presence and the extent of...

Although incretin therapy is clinically available in patients with type 2 diabetes undergoing hemodialysis, no study has yet examined whether incretin therapy is capable of maintaining glycemic control in this group of patients when switched from insulin therapy. In this study, we examined the efficacy of incretin therapy in patients with insulin-t...

Dipeptyl peptidase-4 (DPP-4) inhibitors modulate the progression of atherosclerosis. To gain insights into their mechanism of action, 9-wk-old male apolipoprotein E (apoE)-deficient mice were fed a DPP-4 inhibitor, anagliptin-containing diet. The effects of anagliptin were investigated in, a monocyte cell line, human THP-1 cells, and rat smooth mus...

Dietary habits are associated with obesity, and both are important contributing factors to lifestyle-related diseases. The STYLIST study examined the effects of dietary counseling by registered dietitians and the delivery of proper calorie-controlled meals (UMIN Registration No: 000006582). Two-hundred adult patients with hypertension and/or diabet...