Masato Kasuga

Association Study of the Effect of WFS1 Polymorphisms on Risk of Type 2 Diabetes in Japanese Population (2008)

Mita,Masaki, Miyake,Kazuaki, Zenibayashi,Masako, Hirota,Yushi, Teranishi,Tetsuya, Kouyama,Kunichi, ...

Mutations of WFS1 gene cause Wolfram syndrome, which is a rare autosomalrecessive disorder characterized by juvenile diabetes mellitus, optic atrophy, deafnessand diabetes insipidus. The product...

Role of Hepatic STAT3 in the Regulation of Lipid Metabolism (2008)

Kinoshita,Shinichi, Ogawa,Wataru, Okamoto,Yasuo, Takashima,Mototsugu, Inoue,Hiroshi, Matsuki,Yasushi, ...

Regulation of hepatic gene expression is largely responsible for the control ofnutrient metabolism. We previously showed that the transcription factor STAT3regulates glucose homeostasis by...

Insulin-stimulated Fusion of GLUT4 Vesicles to Plasma Membrane is Dependent on Wortmannin-sensitive Insulin Signaling Pathway in 3T3-L1 Adipocytes (2008)

Kawaguchi,Takayuki, Tamori,Yoshikazu, Yoshikawa,Mari, Kanda,Hajime, Kasuga,Masato

It is established that wortmannin which completely inhibits class IA PI 3-kinaseactivation abrogated the insulin-dependent translocation of GLUT4 to the plasmamembrane in adipocytes and skeletal...

Pancreatic β Cell Mass Preserved in Heterozygous PDK1 Knockout Mice (2008)

Takeda, Akihiko, Kido, Yoshiaki, Hashimoto, Naoko, Noda, Tetsuo, Kasuga, Masato

We have demonstrated that 3-phosphoinositide-dependent protein kinase 1 (PDK1)contributes to signaling by insulin or insulin-like growth fctor-1 (IGF-1) that isresponsible for the regulation of both...

Reduced Insulin Signaling and Endoplasmic Reticulum Stress Act Synergistically to Deteriorate Pancreatic β Cell Function (2008)

Matsuda, Tomokazu, Kido, Yoshiaki, Uchida, Tohru, Kasuga, Masato

The total pancreatic β cell mass is reduced in individuals with type 2 diabetes. Weanalyzed the islets of leptin receptor-deficient (Lepr-/-) mice, a model animal for type 2diabetes with obesity....

Insulin-induced GLUT4 Movements in C2C12 Myoblasts : Evidence against a Role of Conventional Kinesin Motor Proteins (2008)

Takazawa, Kazuo, Noguchi, Tetsuya, Hosooka, Tetsuya, Yoshioka, Toyo, Tobimatsu, Kazutoshi, Kasuga, Masato

Insulin induces translocation of the glucose transporter GLUT4 from intracellularstorage compartment to the plasma membrane via complex mechanisms that requireintact cytoskeletal networks. In...

Taurine Administration after Appearance of Proteinuria Retards Progression of Diabetic Nephropathy in Rats (2008)

Higo, Satomi, Miyata, Satoshi, QING YUN JIANG, Kitazawa, Riko, Kitazawa, Sohei, Kasuga, Masato

Oxidative stress has been postulated to be involved in the development of diabeticnephropathy. In the present study, we evaluated the effect of taurine, an endogenousantioxidant, on diabetic...

Diet-Induced Up-Regulation of Gene Expression in Adipocytes Without Changes in DNA Methylation (2008)

Okada, Yuko, Sakaue, Hiroshi, Nagare, Tomoki, Kasuga, Masato

The expansion of white adipose tissue (WAT) mass during the development ofobesity is mediated in part through an increase in adipocyte size. Although geneexpression profiles associated with...

Methylglyoxal Induces Prostaglandin E2 Production in Rat Mesangial Cells (2007)

Uriuhara, Atsuko, Miyata, Satoshi, Liu, BING-FEN, Miyazaki, Hiroyuki, Kusunoki, Hitomi, Kojima, Hiroshi, ...

The formation of methylglyoxal (MG), a reactive dicarbonyl compound, isaccelerated under hyperglycemia, presumably contributing to tissue injury in diabetes.On the other hand, prostaglandin E2 (PGE2)...

Association of Serum MCP-1 Concentration and MCP-1 Polymorphism with Insulin Resistance in Japanese Individuals with Obese type 2 Diabetes (2007)

Kouyama, Kunichi, Miyake, Kazuaki, Zenibayashi, Masako, Hirota, Yushi, Teranishi, Tetsuya, Tamori, Yoshikazu, ...

Monocyte chemoattractant protein-1 (MCP-1, also known as CCL2) secreted byadipocytes is a member of the CC chemokine family and plays a pivotal role in theinflammatory process. A polymorphism, the...

Insulin Efficiently Stores Triglycerides in Adipocytes by Inhibiting Lipolysis and Repressing PGC-1α Induction. (2007)

Nishino, Naonobu, Tamori, Yoshikazu, Kasuga, Masato

White adipose tissue (WAT) is important as an energy reservoir in mammals, butthe precise mechanism by which energy storage in WAT is controlled remains unclear.It is well known that representative...

Overexpression of thioredoxin1 in transgenic mice suppresses development of diabetic nephropathy (2007)

Hamada, Yasuhiro, Miyata, Satoshi, Nii-Kono, Tomoko, Kitazawa, Riko, Kitazawa, Sohei, Higo, Satomi, ...

Background. Oxidative stress has been suggested to play an important role in the pathogenesis of diabetic nephropathy. In the present study, the effects of thioredoxin1 (TRX1) overexpression, a small...

Overexpression of thioredoxin1 in transgenic mice suppresses development of diabetic nephropathy (2007)

Hamada, Yasuhiro, Miyata, Satoshi, Nii-Kono, Tomoko, Kitazawa, Riko, Kitazawa, Sohei, Higo, Satomi, ...

Background. Oxidative stress has been suggested to play an important role in the pathogenesis of diabetic nephropathy. In the present study, the effects of thioredoxin1 (TRX1) overexpression, a small...

A series of maturity onset diabetes of the young, type 2 (MODY2) mouse models generated by a large-scale ENU mutagenesis program (2004)

Inoue, Maki, Sakuraba, Yoshiyuki, Motegi, Hiromi, Kubota, Naoto, Toki, Hideaki, Matsui, Junko, ...

Mutant mouse models are indispensable tools for clarifying the functions of genes and for elucidating the underlying pathogenic mechanisms of human diseases. Currently, several large-scale...

A series of maturity onset diabetes of the young, type 2 (MODY2) mouse models generated by a large-scale ENU mutagenesis program (2004)

Inoue, Maki, Sakuraba, Yoshiyuki, Motegi, Hiromi, Kubota, Naoto, Toki, Hideaki, Matsui, Junko, ...

Mutant mouse models are indispensable tools for clarifying the functions of genes and for elucidating the underlying pathogenic mechanisms of human diseases. Currently, several large-scale...

IFN-alpha prevents the growth of pre-neoplastic lesions and inhibits the development of hepatocellular carcinoma in the rat (2004)

Nakaji, Miyuki, Yano, Yoshihiko, Ninomiya, Toshiaki, Seo, Yasushi, Hamano, Kenichi, Yoon, Seitetsu, ...

Interferon (IFN)-alpha treatment is a common therapy for chronic viral hepatitis and contributes to preventing hepatocarcinogenesis. However, it is not clear whether IFN-alpha directly inhibits the...

A series of maturity onset diabetes of the young, type 2 (MODY2) mouse models generated by a large-scale ENU mutagenesis program (2004)

Inoue, Maki, Sakuraba, Yoshiyuki, Motegi, Hiromi, Kubota, Naoto, Toki, Hideaki, Matsui, Junko, ...

Mutant mouse models are indispensable tools for clarifying the functions of genes and for elucidating the underlying pathogenic mechanisms of human diseases. Currently, several large-scale...

IFN-alpha prevents the growth of preneoplastic lesions and inhibits the development of hepatocellular carcinoma in the rat (2003)

Nakaji, Miyuki, Yano, Yoshihiko, Ninomiya, Toshiaki, Seo, Yasushi, Hamano, Kenichi, Yoon, Seitetsu, ...

Interferon (IFN) -alpha treatment is a common therapy for chronic viral hepatitis and contributes to preventing hepatocarcinogenesis. However, it is not clear whether IFN-alpha directly inhibits the...

IFN-alpha prevents the growth of preneoplastic lesions and inhibits the development of hepatocellular carcinoma in the rat (2003)

Nakaji, Miyuki, Yano, Yoshihiko, Ninomiya, Toshiaki, Seo, Yasushi, Hamano, Kenichi, Yoon, Seitetsu, ...

Interferon (IFN) -alpha treatment is a common therapy for chronic viral hepatitis and contributes to preventing hepatocarcinogenesis. However, it is not clear whether IFN-alpha directly inhibits the...

Differential Control of Cellular Gene Expression by Diffusible and Non-Diffusible EGF (2001)

Ito, Yoshihiro, Chen, Guoping, Imanishi, Yukio, Morooka, Takaya, Nishida, Eisuke, Okabayashi, Yoshinori, ...

Cell gene expression is affected by both the kind and mode of growth factor stimulation (diffusive vs. non-diffusive). Epidermal growth factor (EGF) was pattern-immobilized on a polystyrene plate....

Enhancement of the Mitogenic Effect by Artificial Juxtacrine Stimulation Using Immobilized EGF (1997)

Ito, Yoshihiro, Li, Jing-Song, Takahashi, Takashi, Imanishi, Yukio, Okabayashi, Yoshinori, Kido, Yoshiaki, ...

Mouse epidermal growth factor (EGF) was covalently conjugated with the water-soluble polymer, poly(acrylic acid) (EGF-PAA), or with the water-insoluble polymer, surface-hydrolyzed poly(methyl...

Prevention of autoimmune insulin-dependent diabetes in non-obese diabetic mice by anti-LFA-1 and anti-ICAM-1 mAb (1994)

Hasegawa, Yutaka, Yokono, Koichl, Taki, Toshiya, Amano, Kazuhiko, Tominaga, Yolchi, Yoneda, Ryoji, ...

Diverse adhesion molecules participate in many important responses and thus would be implicated in the pathogenesis of various autoimmune diseases. However, there is little evidence for the role of...

Regulation of nuclear translocation of Forkhead transcription factor AFX by protein kinase B

Takaishi, Hiroshi, Konishi, Hiroaki, Matsuzaki, Hidenori, Ono, Yoshitaka, Shirai, Yasuhito, Saito, Naoaki, ...

The regulation of intracellular localization of AFX, a human Forkhead transcription factor, was studied. AFX was recovered as a phosphoprotein from transfected COS-7 cells growing in the presence of...

Insulin-Induced Phosphorylation and Activation of Cyclic Nucleotide Phosphodiesterase 3B by the Serine-Threonine Kinase Akt

Kitamura, Tadahiro, Kitamura, Yukari, Kuroda, Shoji, Hino, Yasuhisa, Ando, Miwa, Kotani, Ko, ...

Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the cellular concentrations of the second messengers cyclic AMP (cAMP) and cGMP. Insulin activates the 3B isoform of PDE in...

Inhibition of the Motility and Growth of B16F10 Mouse Melanoma Cells by Dominant Negative Mutants of Dok-1

Hosooka, Tetsuya, Noguchi, Tetsuya, Nagai, Hiroshi, Horikawa, Tatsuya, Matozaki, Takashi, Ichihashi, Masamitsu, ...

Dok-1 (p62Dok) is a multiple-site docking protein that acts downstream of receptor and nonreceptor tyrosine kinases. Although it has been proposed to contribute to the control of cell growth and...

Requirement for Activation of the Serine-Threonine Kinase Akt (Protein Kinase B) in Insulin Stimulation of Protein Synthesis but Not of Glucose Transport

Kitamura, Tadahiro, Ogawa, Wataru, Sakaue, Hiroshi, Hino, Yasuhisa, Kuroda, Shoji, Takata, Masafumi, ...

A wide variety of biological activities including the major metabolic actions of insulin is regulated by phosphatidylinositol (PI) 3-kinase. However, the downstream effectors of the various signaling...

Requirement of Atypical Protein Kinase Cλ for Insulin Stimulation of Glucose Uptake but Not for Akt Activation in 3T3-L1 Adipocytes

Kotani, Ko, Ogawa, Wataru, Matsumoto, Michihiro, Kitamura, Tadahiro, Sakaue, Hiroshi, Hino, Yasuhisa, ...

Phosphoinositide (PI) 3-kinase contributes to a wide variety of biological actions, including insulin stimulation of glucose transport in adipocytes. Both Akt (protein kinase B), a serine-threonine...

Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver

Miyake, Kazuaki, Ogawa, Wataru, Matsumoto, Michihiro, Nakamura, Takehiro, Sakaue, Hiroshi, Kasuga, Masato

The physiological relevance of phosphoinositide 3-kinase (PI 3-K) signaling in the liver to fuel homeostasis was investigated. Systemic infusion of an adenovirus encoding a dominant negative mutant...

Requirement of fibroblast growth factor 10 in development of white adipose tissue

Sakaue, Hiroshi, Konishi, Morichika, Ogawa, Wataru, Asaki, Toshiyuki, Mori, Toshiyuki, Yamasaki, Masahiro, ...

Fibroblast growth factors (FGFs) are important intercellular signaling molecules in developmental processes. Here, we show that FGF10 is secreted by cultured preadipocytes and that prevention of...

PKCλ in liver mediates insulin-induced SREBP-1c expression and determines both hepatic lipid content and overall insulin sensitivity

Matsumoto, Michihiro, Ogawa, Wataru, Akimoto, Kazunori, Inoue, Hiroshi, Miyake, Kazuaki, Furukawa, Kensuke, ...

PKCλ is implicated as a downstream effector of PI3K in insulin action. We show here that mice that lack PKCλ specifically in the liver (L-λKO mice), produced with the use of the Cre-loxP system,...

SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility

Inagaki, Kenjiro, Yamao, Takuji, Noguchi, Tetsuya, Matozaki, Takashi, Fukunaga, Kaoru, Takada, Toshiyuki, ...

The transmembrane glycoprotein SHPS-1 binds the protein tyrosine phosphatase SHP-2 and serves as its substrate. Although SHPS-1 has been implicated in growth factor- and cell adhesion-induced...

PKCλ regulates glucose-induced insulin secretion through modulation of gene expression in pancreatic β cells

Hashimoto, Naoko, Kido, Yoshiaki, Uchida, Tohru, Matsuda, Tomokazu, Suzuki, Kazuhisa, Inoue, Hiroshi, ...

Altered regulation of insulin secretion by glucose is characteristic of individuals with type 2 diabetes mellitus, although the mechanisms that underlie this change remain unclear. We have now...

Adipocytes from Munc18c-null mice show increased sensitivity to insulin-stimulated GLUT4 externalization

Kanda, Hajime, Tamori, Yoshikazu, Shinoda, Hiroaki, Yoshikawa, Mari, Sakaue, Motoyoshi, Udagawa, Jun, ...

Insulin-stimulated glucose uptake in adipocytes is mediated by translocation of vesicles containing the glucose transporter GLUT4 from intracellular storage sites to the cell periphery and the...

MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity

Kanda, Hajime, Tateya, Sanshiro, Tamori, Yoshikazu, Kotani, Ko, Hiasa, Ken-ichi, Kitazawa, Riko, ...

Adipocytes secrete a variety of bioactive molecules that affect the insulin sensitivity of other tissues. We now show that the abundance of monocyte chemoattractant protein–1 (MCP-1) mRNA in...

Insulin resistance and pancreatic β cell failure

Kasuga, Masato

It is now well accepted that diabetes mellitus is one of the main threats to human health in the twenty-first century. The total number of people with diabetes worldwide was estimated at between 151...

Regulation of nuclear translocation of Forkhead transcription factor AFX by protein kinase B

Takaishi, Hiroshi, Konishi, Hiroaki, Matsuzaki, Hidenori, Ono, Yoshitaka, Shirai, Yasuhito, Saito, Naoaki, ...

The regulation of intracellular localization of AFX, a human Forkhead transcription factor, was studied. AFX was recovered as a phosphoprotein from transfected COS-7 cells growing in the presence of...

Insulin-Induced Phosphorylation and Activation of Cyclic Nucleotide Phosphodiesterase 3B by the Serine-Threonine Kinase Akt

Kitamura, Tadahiro, Kitamura, Yukari, Kuroda, Shoji, Hino, Yasuhisa, Ando, Miwa, Kotani, Ko, ...

Cyclic nucleotide phosphodiesterase (PDE) is an important regulator of the cellular concentrations of the second messengers cyclic AMP (cAMP) and cGMP. Insulin activates the 3B isoform of PDE in...

Inhibition of the Motility and Growth of B16F10 Mouse Melanoma Cells by Dominant Negative Mutants of Dok-1

Hosooka, Tetsuya, Noguchi, Tetsuya, Nagai, Hiroshi, Horikawa, Tatsuya, Matozaki, Takashi, Ichihashi, Masamitsu, ...

Dok-1 (p62Dok) is a multiple-site docking protein that acts downstream of receptor and nonreceptor tyrosine kinases. Although it has been proposed to contribute to the control of cell growth and...

Requirement for Activation of the Serine-Threonine Kinase Akt (Protein Kinase B) in Insulin Stimulation of Protein Synthesis but Not of Glucose Transport

Kitamura, Tadahiro, Ogawa, Wataru, Sakaue, Hiroshi, Hino, Yasuhisa, Kuroda, Shoji, Takata, Masafumi, ...

A wide variety of biological activities including the major metabolic actions of insulin is regulated by phosphatidylinositol (PI) 3-kinase. However, the downstream effectors of the various signaling...

Requirement of Atypical Protein Kinase Cλ for Insulin Stimulation of Glucose Uptake but Not for Akt Activation in 3T3-L1 Adipocytes

Kotani, Ko, Ogawa, Wataru, Matsumoto, Michihiro, Kitamura, Tadahiro, Sakaue, Hiroshi, Hino, Yasuhisa, ...

Phosphoinositide (PI) 3-kinase contributes to a wide variety of biological actions, including insulin stimulation of glucose transport in adipocytes. Both Akt (protein kinase B), a serine-threonine...

Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver

Miyake, Kazuaki, Ogawa, Wataru, Matsumoto, Michihiro, Nakamura, Takehiro, Sakaue, Hiroshi, Kasuga, Masato

The physiological relevance of phosphoinositide 3-kinase (PI 3-K) signaling in the liver to fuel homeostasis was investigated. Systemic infusion of an adenovirus encoding a dominant negative mutant...

Requirement of fibroblast growth factor 10 in development of white adipose tissue

Sakaue, Hiroshi, Konishi, Morichika, Ogawa, Wataru, Asaki, Toshiyuki, Mori, Toshiyuki, Yamasaki, Masahiro, ...

Fibroblast growth factors (FGFs) are important intercellular signaling molecules in developmental processes. Here, we show that FGF10 is secreted by cultured preadipocytes and that prevention of...

PKCλ in liver mediates insulin-induced SREBP-1c expression and determines both hepatic lipid content and overall insulin sensitivity

Matsumoto, Michihiro, Ogawa, Wataru, Akimoto, Kazunori, Inoue, Hiroshi, Miyake, Kazuaki, Furukawa, Kensuke, ...

PKCλ is implicated as a downstream effector of PI3K in insulin action. We show here that mice that lack PKCλ specifically in the liver (L-λKO mice), produced with the use of the Cre-loxP system,...

SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility

Inagaki, Kenjiro, Yamao, Takuji, Noguchi, Tetsuya, Matozaki, Takashi, Fukunaga, Kaoru, Takada, Toshiyuki, ...

The transmembrane glycoprotein SHPS-1 binds the protein tyrosine phosphatase SHP-2 and serves as its substrate. Although SHPS-1 has been implicated in growth factor- and cell adhesion-induced...

PKCλ regulates glucose-induced insulin secretion through modulation of gene expression in pancreatic β cells

Hashimoto, Naoko, Kido, Yoshiaki, Uchida, Tohru, Matsuda, Tomokazu, Suzuki, Kazuhisa, Inoue, Hiroshi, ...

Altered regulation of insulin secretion by glucose is characteristic of individuals with type 2 diabetes mellitus, although the mechanisms that underlie this change remain unclear. We have now...

Adipocytes from Munc18c-null mice show increased sensitivity to insulin-stimulated GLUT4 externalization

Kanda, Hajime, Tamori, Yoshikazu, Shinoda, Hiroaki, Yoshikawa, Mari, Sakaue, Motoyoshi, Udagawa, Jun, ...

Insulin-stimulated glucose uptake in adipocytes is mediated by translocation of vesicles containing the glucose transporter GLUT4 from intracellular storage sites to the cell periphery and the...

MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity

Kanda, Hajime, Tateya, Sanshiro, Tamori, Yoshikazu, Kotani, Ko, Hiasa, Ken-ichi, Kitazawa, Riko, ...

Adipocytes secrete a variety of bioactive molecules that affect the insulin sensitivity of other tissues. We now show that the abundance of monocyte chemoattractant protein–1 (MCP-1) mRNA in...

Insulin resistance and pancreatic β cell failure

Kasuga, Masato

It is now well accepted that diabetes mellitus is one of the main threats to human health in the twenty-first century. The total number of people with diabetes worldwide was estimated at between 151...

VEGF T-1498C polymorphism, a predictive marker of differentiation of colorectal adenocarcinomas in Japanese

Yamamori, Motohiro, Taniguchi, Mayuko, Maeda, Shingo, Nakamura, Tsutomu, Okamura, Noboru, Kuwahara, Akiko, ...

Background: Previously, MDR1 T-129C polymorphism, encoding multidrug resistant transporter MDR1/P-glycoprotein, was reported to be predictive of poorly-differentiated colorectal adenocarcinomas....

FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets

Nishino, Naonobu, Tamori, Yoshikazu, Tateya, Sanshiro, Kawaguchi, Takayuki, Shibakusa, Tetsuro, Mizunoya, Wataru, ...

White adipocytes are unique in that they contain large unilocular lipid droplets that occupy most of the cytoplasm. To identify genes involved in the maintenance of mature adipocytes, we expressed...

Biphasic Response of Pancreatic β-Cell Mass to Ablation of Tuberous Sclerosis Complex 2 in Mice▿

Shigeyama, Yutaka, Kobayashi, Toshiyuki, Kido, Yoshiaki, Hashimoto, Naoko, Asahara, Shun-ichiro, Matsuda, Tomokazu, ...

Recent studies have demonstrated the importance of insulin or insulin-like growth factor 1 (IGF-1) for regulation of pancreatic β-cell mass. Given the role of tuberous sclerosis complex 2 (TSC2) as...