Noriyuki Iwamoto

Eli Lilly

The ATP-binding cassette transporter ABCA1 plays an essential role in the formation of high-density lipoprotein (HDL) by mediating phospholipid and cholesterol efflux to apolipoprotein A-I. In humans, loss-of-function mutations in the ABCA1 gene cause Tangier disease (TD), a familial HDL deficiency. In addition to the disappearance of HDL, TD patie...

IntroductionThis analysis investigated the relationship between baseline fasting pancreatic β-cell function and efficacy in Japanese patients with type 2 diabetes (T2D) treated with once-weekly dulaglutide 0.75 mg (dulaglutide) or once-daily liraglutide 0.9 mg (liraglutide) for up to 52 weeks. Methods In a 52-week study of monotherapy in Japanese p...

The primary goal of the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) was to assess the safety and effectiveness of Humatrope®, a GH preparation, in the treatment of pediatric patients with short stature. We report our findings in the GH-treated Japanese pediatric population focusing on the incidence of type 2 diabe...

In Japan, premixed insulins are commonly used as starter insulin for type 2 diabetes. This subpopulation analysis assessed the efficacy and safety of twice-daily LM25 (25% insulin lispro/75% insulin lispro protamine) and LM50 (50% insulin lispro/50% insulin lispro protamine) as starter insulin in Japanese subjects, and compared these results with t...

We analyzed the efficacy and safety of once weekly dulaglutide 0.75 mg by sex in 2 randomized, controlled phase 3 studies in Japanese patients with type 2 diabetes (a 52-week monotherapy study [comparator liraglutide 0.9 mg] and a 26-week combination therapy study [comparator insulin glargine]). Females comprised 18% of patients in the monotherapy...

Table S1 | Least squares mean change from baseline in self‐monitored blood glucose levels. Table S2 | Least squares mean change from baseline in 1,5‐anhydroglucitol. Table S3 | Least squares mean change from baseline in glycated hemoglobin. Table S4 | Seven‐point self‐monitored blood glucose levels for participants treated with 25% insulin lispr...

Figure S1 | Seven‐point self‐monitored blood glucose levels for participants with type 2 diabetes mellitus treated with 25% insulin lispro/75% insulin lispro protamine suspension or 50% insulin lispro/50% insulin lispro protamine suspension at baseline and at end‐point.

The effects of incretin therapies on pancreatic safety are currently being evaluated. In 3 phase 3 clinical studies of once weekly dulaglutide 0.75 mg (dulaglutide) in Japanese patients with type 2 diabetes (T2D), symptoms suggestive of acute pancreatitis as well as pancreatic enzymes were assessed and the risk of acute pancreatitis was evaluated....

Background and aims: Expression of ATP binding cassette transporter (ABC) A1, a key membrane protein for biogenesis of high-density lipoprotein (HDL), is regulated not only by its gene transcription but also by its intracellular degradation to modulate plasma HDL concentration. We previously showed that inhibition of ABCA1 degradation by probucol...

Aims/introduction: The pathophysiology of diabetes differs between Asian and Western patients in many ways, and diet is a primary contributor. This study examined the effect of diet on the efficacy of 25% insulin lispro/75% insulin lispro protamine (LM25) and 50% insulin lispro/50% insulin lispro protamine (LM50) as starter insulin in Chinese and...

Objective: Lispro Mix 25% insulin lispro/75% insulin lispro protamine (LM25 ) and Lispro Mix 50% insulin lispro/50% insulin lispro protamine (LM50) were compared as starter insulins in East Asian-dominated patients with type 2 diabetes. Research Design and Methods Phase 4, open-label, randomized trial conducted in China, Japan, Korea, and Turkey....

Figure S1. Updated homoeostasis model assessment changes from baseline at week 52 (LOCF). Table S1. Summary of least squares (±standard error) mean changes from baseline in self‐monitored blood glucose (mmol/l) values (LOCF at week 52). Table S2. Summary of serious adverse events by preferred term and treatment for the treatment period from basel...

The efficacy and tolerability of once weekly dulaglutide 0.75 mg in Japanese patients with type 2 diabetes (T2D) were evaluated by subgroups defined by key demographic characteristics. This post hoc analysis included data from patients who received dulaglutide 0.75 mg for up to 26 weeks in three phase 3 trials (one open-label, randomized; one doubl...

Aims: To examine the efficacy and safety of once weekly dulaglutide 0.75 mg monotherapy compared with once daily liraglutide 0.9 mg in Japanese patients with type 2 diabetes (T2D) for 52 weeks. Primary results (after 26 weeks) have been reported. Methods: This was a phase III, randomized, 52-week (26-week primary endpoint), active- and placebo-c...

Table S2. Summary of serious adverse events by preferred term and treatment for the treatment period from baseline to 26 weeks.

Table S4. Summary and analysis of lipid profiles: median baseline values and median absolute and percent changes from baseline to 26 weeks (LOCF).

Table S3. Summary and analysis of renal analytes: median baseline values and median changes from baseline to 26 weeks (LOCF).

Figure S1. Updated homeostasis model assessment changes from baseline at 26 weeks (LOCF).

Table S1. Summary of least squares (± standard error) mean changes from baseline in self‐monitored blood glucose (mmol/l) values (LOCF at week 26).

Cellular cholesterol homeostasis involves sterol sensing at the endoplasmic reticulum (ER) and sterol export from the plasma membrane (PM). Sterol sensing at the ER requires efficient sterol delivery from the PM; however, the macromolecules that facilitate retrograde sterol transport at the PM have not been identified. ATP-binding cassette transpor...

We examined the efficacy and safety of once weekly dulaglutide monotherapy (0.75 mg) (dulaglutide) compared to placebo and once daily liraglutide (0.9 mg) (liraglutide) in Japanese patients with type 2 diabetes. This was a phase 3, 52-week (26-week primary endpoint), randomised, double-blind, placebo-controlled, open-label comparator (liraglutide)...

In addition to impaired physical activity, adult GH deficiency (GHD) can decrease quality of life (QOL). Hence, assessment of QOL is important to evaluate the efficacy of GH replacement therapy. This study aimed to identify factors that may be predictive of long-term improvement in QOL among clinical/laboratory variables during GH replacement thera...

The aim of this study was to assess changes in quality of life (QoL) in Japanese children with GH deficiency (GHD) after 12 mo of GH treatment or with idiopathic short stature (ISS) after 12 mo without treatment. Children with GHD were treated with GH after enrollment. Outcome measures included the parent-rated Child Behavior Checklist (CBCL), the...

Low-density lipoprotein apheresis (LDL-A) treatment has been shown to decrease serum LDL cholesterol levels and prevent cardiovascular events in homozygous patients with familial hypercholesterolemia. Recently, LDL-A treatment has been suggested to have beneficial effects beyond the removal of LDL particles. In this study, to clarify the preventive...

Heterozygous patients with familial hypercholesterolemia (FH) are known to be associated with a high risk of coronary artery disease (CAD), which is a major determinant of their clinical outcome. The prognosis of heterozygous FH patients substantially varies, being dependent on the level of their CAD risk, and their therapeutic regimen should be in...

Advances in nanotechnology have led to its application in the field of biomaterials, including drug delivery systems (DDS). To carry nucleic acid drugs, other drugs, and genes to the targeted organs, devices that can carry them intact all the way from the site of administration to the target organs are needed. The development of DDS materials is a...

We recently reported that the endogenous ATP-binding cassette transporter (ABC) A7 strongly associates with phagocytosis, being regulated by sterol regulatory element binding protein 2. We therefore examined the effect of statins on phagocytosis in vitro and in vivo through the SREBP-ABCA7. Phagocytosis was found to be enhanced by pravastatin, rosu...

Helical apolipoproteins remove cellular phospholipid and cholesterol to generate nascent HDL and this reaction is the major source of plasma HDL. ABCA1 is mandatory and rate-limiting for this reaction. Besides regulation of the gene expression by transcriptional factors including LXR, AP2 and SREBP, the ABCA1 activity is regulated post-translationa...

Expression of the activator protein (AP) 2β is closely associated with type-2 diabetes and negatively regulates expression of the adiponectin gene. We previously demonstrated that AP-2α negatively regulates the ATP-binding cassette A1 (ABCA1) gene through its Ser-phosphorylation by protein kinase (PK) D. The phosphorylation site of AP-2α located in...

ATP-binding cassette transporter (ABC) A7 is an ABC family protein that is a so-called full-size ABC transporter, highly homologous to ABCA1, which mediates the biogenesis of high-density lipoprotein (HDL) with cellular lipid and helical apolipoproteins. ABCA7 mediates the formation of HDL when exogenously transfected and expressed; however, endoge...

We previously reported that the endogenous ATP-binding cassette transporter (ABC)A7 strongly associates with phagocytic function rather than biogenesis of high-density lipoprotein (HDL), being regulated by sterol-regulatory element binding protein (SREBP)2. Phagocytic activity was found enhanced by apolipoprotein (apo)A-I and apoA-II more than twic...

To investigate the interaction of ATP-binding cassette transporter A1 (ABCA1) with calmodulin in relation to its calpain-mediated degradation because many calpain substrates bind calmodulin to regulate cellular functions. The activity of ABCA1 is regulated through proteolysis by calpain. An immunoprecipitation and glutathione S-transferase pull-dow...

Expression of ABCA1 is regulated by transcription of the gene and calpain-mediated proteolytic degradation, and inhibition ABCA1 degradation results in increased ABCA1 and HDL biogenesis in vitro. We examined whether this approach could be a potential antiatherogenic treatment. Although probucol inhibits both the activity and degradation of ABCA1,...

Fibroblast growth factor 1 (FGF-1) enhances apolipoprotein E (apoE) expression and apoE-HDL biogenesis in autocrine fashion in astrocytes (Ito, J., Y. Nagayasu, R. Lu, A. Kheirollah, M. Hayashi, and S. Yokoyama. Astrocytes produce and secrete FGF-1, which promotes the production of apoE-HDL in a manner of autocrine action. J. Lipid Res. 2005. 46: 6...

Activator protein (AP) 2alpha negatively regulates expression of ABCA1 gene through Ser-phosphorylation of AP2alpha (Circ Res. 2007;101:156-165). Potential specific Ser-phosphorylation sites for this reaction were investigated in human AP2alpha. The phosphorylation was shown mediated by PKD, and Ser258 and Ser326 were found in its specific phosphor...

Calpain-mediated proteolysis is one of the major regulatory factors for activity of ATP-binding cassette transporter (ABC) A1. Helical apolipoproteins protect ABCA1 against this degradation and increase generation of HDL. We investigated the mechanism for this reaction focusing on roles of endocytotic internalization of ABCA1. Surface ABCA1 was lab...

Serum amyloid A (SAA) was markedly increased in the plasma and in the liver upon acute inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS) in mice, and SAA in the plasma was exclusively associated with HDL. In contrast, no HDL was present in the plasma and only a small amount of SAA was found in the VLDL/LDL fraction (d <...

ATP-binding cassette transporter A1 (ABCA1) is a rate-limiting factor for high-density lipoprotein (HDL) biogenesis. The ABCA1 gene expression is known to be upregulated by various transcriptional factors. However, negative regulation factors would be better targets for pharmacological modulation of HDL biogenesis. Doxazosin, an alpha(1)-adrenocept...

The ATP binding cassette transporters A1 and G1 (ABCA1/G1) and scavenger receptor class B type I (SR-BI) are key molecules in cholesterol efflux and atherogenesis. These genes are regulated by peroxisome proliferator-activated receptor gamma (PPARgamma) and liver X receptor (LXR). Telmisartan is an angiotensin type 1 receptor blocker which has been...

ABCA7 is highly homologous to ABCA1 and mediates cellular cholesterol and phospholipid release by apolipoproteins when transfected in vitro. However, expression of ABCA7 was downregulated by increased cellular cholesterol while ABCA1 was upregulated, and the results were consistent by forced expression or downregulation of sterol-responsive/regulat...

Serum amyloid A (SAA) is an amphiphilic helical protein that is found associated with plasma HDL in various pathological conditions, such as acute or chronic inflammation. Cellular lipid release and generation of HDL by this protein were investigated, in comparison with the reactions by apolipoprotein A-I (apoA-I) and several types of cells that ap...

The ATP-binding cassette transporter-A1 (ABCA1) regulates cholesterol efflux from cells and is involved in high-density lipoprotein metabolism and atherogenesis. The objective of this study was to investigate the effect of dexamethasone (Dex) and other glucocorticoid receptor (GR) ligands on apolipoprotein AI-mediated cholesterol efflux from macrop...

We sought to elucidate the effects of 20-mg versus 5-mg atorvastatin on thoracic and abdominal aortic plaques. Regression of thoracic aortic plaques by simvastatin was demonstrated using magnetic resonance imaging (MRI). However, the effects of different doses of statin have not been assessed. Using MRI, we investigated the effects of 20-mg versus...

TLRs are receptors involved in the recognition of pathogens by the innate immune system, and TLR2 and TLR4 play important roles in the activation of monocytes. A total of 105 consecutive patients who underwent coronary angiography comprised of 46 with stable effort angina (SA), 41 with unstable angina (UA), and 18 with no significant CAD (CNT) were...

Background Although cholesterol management reportedly reduces fatal and non-fatal coronary heart disease (CHD) events in subjects with or without evident atherosclerotic disease, it is still uncertain whether these benefits extend to Japanese. Methods and Results The study group comprised 8,009 subjects with mildly elevated total cholesterol who we...

Nonalcoholic steatohepatitis (NASH) is associated with the metabolism of lipid, glucose and energy. Beta-adrenergic receptors play an important role in the regulation of energy expenditure, in part, by stimulating lipid mobilization through lipolysis. To assess whether it is common for the beta2-adrenergic receptor (B2AR) gene polymorphisms in codo...

CD36 deficiency is reportedly an underlying factor about insulin resistance, defective fatty acid metabolism and hypertriglyceridemia in spontaneously hypertensive rat (SHR), and may be involved in the pathogenesis of insulin resistance and hyperlipidemia in humans. We examined 831 adults undergoing health screening. The majority (780) was Pro90 ho...

We determined the effects of soy protein isolate (SPI) intake on remnant-like particles (RLP), lipolytic enzymes, lipid transfer protein, transaminases, sex hormones, iron, calcium, and vitamin E in healthy men. In the first randomized, crossover experiment, 14 men were given either 20 g per day of SPI or nothing (control) for each 4-week segment....