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Article ; Online: New perspectives on insulin therapy.

Araki, Eiichi / Araki, Hirotaka / Senokuchi, Takafumi / Motoshima, Hiroyuki

2020 Volume 11, Issue 4, Page(s) 795–797

MeSH term(s)	Diabetes Mellitus/drug therapy ; Glycemic Control/methods ; Glycemic Control/trends ; Humans ; Hypoglycemic Agents/therapeutic use ; Insulins/therapeutic use
Chemical Substances	Hypoglycemic Agents ; Insulins
Language	English
Publishing date	2020-05-21
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2625840-7
ISSN	2040-1124 ; 2040-1116
ISSN (online)	2040-1124
ISSN	2040-1116
DOI	10.1111/jdi.13263
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Article ; Online: Autoimmune Polyglandular Syndrome Type 3 Complicated with IgG4-related Disease.

Murata, Yusuke / Haneda, Masaki / Miyakawa, Nobukazu / Nishida, Saiko / Kajihara, Nobuhiro / Maeda, Sarie / Ono, Kaoru / Hanatani, Satoko / Igata, Motoyuki / Takaki, Yuki / Motoshima, Hiroyuki / Kishikawa, Hideki / Araki, Eiichi

Internal medicine (Tokyo, Japan)

2023 Volume 63, Issue 3, Page(s) 425–431

Abstract: A 52-year-old Japanese woman developed type 1 diabetes mellitus (type 1 DM) at 41 years old. She became complicated with Hashimoto's disease and showed swelling of both submandibular glands, which was diagnosed as IgG4-related disease (IgG4-RD). This is ... ...

Abstract	A 52-year-old Japanese woman developed type 1 diabetes mellitus (type 1 DM) at 41 years old. She became complicated with Hashimoto's disease and showed swelling of both submandibular glands, which was diagnosed as IgG4-related disease (IgG4-RD). This is a rare case of a Japanese patient with autoimmune polyglandular syndrome type 3A (APS-3A) coexisting with autoimmune thyroid disease (AITD) and type 1 DM complicated by IgG4-RD. Bilateral submandibular gland resection was successfully performed without steroid therapy. We discuss the possibility that the immunological pathogenic mechanisms of APS-3A and IgG4-RD are related.
MeSH term(s)	Female ; Humans ; Adult ; Middle Aged ; Immunoglobulin G4-Related Disease/complications ; Immunoglobulin G4-Related Disease/diagnosis ; Polyendocrinopathies, Autoimmune/complications ; Polyendocrinopathies, Autoimmune/diagnosis ; Hashimoto Disease/complications ; Hashimoto Disease/diagnosis ; Diabetes Mellitus, Type 1/complications ; Autoimmune Diseases/complications ; Autoimmune Diseases/diagnosis
Language	English
Publishing date	2023-06-21
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.1270-22
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Article ; Online: Hypoglycemia Induces Mitochondrial Reactive Oxygen Species Production Through Increased Fatty Acid Oxidation and Promotes Retinal Vascular Permeability in Diabetic Mice.

Yoshinaga, Ayaka / Kajihara, Nobuhiro / Kukidome, Daisuke / Motoshima, Hiroyuki / Matsumura, Takeshi / Nishikawa, Takeshi / Araki, Eiichi

Antioxidants & redox signaling

2020 Volume 34, Issue 16, Page(s) 1245–1259

Abstract: Aims: ...

Abstract	Aims:
MeSH term(s)	Animals ; Blood-Retinal Barrier/metabolism ; Capillary Permeability ; Cells, Cultured ; Diabetes Mellitus, Experimental/chemically induced ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/metabolism ; Diabetic Retinopathy/chemically induced ; Diabetic Retinopathy/metabolism ; Disease Models, Animal ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Fatty Acids/metabolism ; Gene Expression Regulation ; Humans ; Hypoglycemia/complications ; Hypoglycemia/metabolism ; Mice ; Mice, Transgenic ; Mitochondria/metabolism ; Reactive Oxygen Species/metabolism ; Retina/cytology ; Retina/metabolism ; Streptozocin/adverse effects ; Superoxide Dismutase/genetics ; Superoxide Dismutase/metabolism ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Fatty Acids ; Reactive Oxygen Species ; Vascular Endothelial Growth Factor A ; vascular endothelial growth factor A, mouse ; Streptozocin (5W494URQ81) ; Superoxide Dismutase (EC 1.15.1.1)
Language	English
Publishing date	2020-08-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2019.8008
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Zs.A 5488: Show issues

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Article ; Online: Aging-associated and CD4 T-cell-dependent ectopic CXCL13 activation predisposes to anti-PD-1 therapy-induced adverse events.

Tsukamoto, Hirotake / Komohara, Yoshihiro / Tomita, Yusuke / Miura, Yuji / Motoshima, Takanobu / Imamura, Kosuke / Kimura, Toshiki / Ikeda, Tokunori / Fujiwara, Yukio / Yano, Hiromu / Kamba, Tomomi / Sakagami, Takuro / Oshiumi, Hiroyuki

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 29, Page(s) e2205378119

Abstract: Clinical success of immune-checkpoint blockade (ICB) cancer immunotherapy is compromised by increased risk of immune-related adverse events (irAEs). However, mechanistic action(s) of immune responses underlying development of irAE remain not fully ... ...

Abstract	Clinical success of immune-checkpoint blockade (ICB) cancer immunotherapy is compromised by increased risk of immune-related adverse events (irAEs). However, mechanistic action(s) of immune responses underlying development of irAE remain not fully explored. Here, we found that in tumor-bearing aged, but not young, mice, antiprogrammed death receptor (PD)-1 therapy elicited irAE-like multiorgan dysfunctions with ectopic accumulation of T and B cells in damaged organs. In this preclinical model, the organ toxicities were mediated by immunoglobulin G (IgG) deposition because administration of IG from ICB-treated aged mice induced the pathogenicity specifically in naïve aged hosts. Mechanistically, CD4 T-cell-derived interleukin (IL)-21 upregulated B-cell-homing chemokine, CXCL13, preferentially in irAE organs from aged mice treated with anti-PD-1 therapy. The ICB-induced pathogenicity was alleviated by B-cell depletion or by blockade of IL-21 or CXCL13 activity. These results suggest that age-associated immune regulatory milieu contributes to the formation of tertiary lymphoid structure-like lymphocytic aggregates in irAE organs and irAE-related toxicity employing IL-21-CXCL13-auto-antibody axis. Supporting this, a systemic increase in CXCL13 and
MeSH term(s)	Aging/immunology ; Animals ; CD4-Positive T-Lymphocytes/immunology ; Chemokine CXCL13/immunology ; Immune Checkpoint Inhibitors/adverse effects ; Immune Checkpoint Inhibitors/therapeutic use ; Immune System Diseases/etiology ; Immunotherapy/adverse effects ; Lymphocyte Activation ; Mice ; Neoplasms/therapy ; Programmed Cell Death 1 Receptor/antagonists & inhibitors
Chemical Substances	Chemokine CXCL13 ; Cxcl13 protein, mouse ; Immune Checkpoint Inhibitors ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2022-07-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2205378119
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Zs.A 1148: Show issues

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Article: [RAAS and insulin resistance].

Motoshima, Hiroyuki / Araki, Eiichi

Nihon rinsho. Japanese journal of clinical medicine

2012 Volume 70, Issue 9, Page(s) 1542–1549

Abstract: The role of the renin-angiotensin-aldosterone system (RAAS) on the development of insulin resistance and type 2 diabetes (T2DM) is an area of growing interest. Most of the deleterious actions of the RAAS on insulin signals appear to be mediated through ... ...

Abstract	The role of the renin-angiotensin-aldosterone system (RAAS) on the development of insulin resistance and type 2 diabetes (T2DM) is an area of growing interest. Most of the deleterious actions of the RAAS on insulin signals appear to be mediated through activation of the serine/threonine kinase, oxidative stress and tissue-inflammation in insulin-sensitive organs. Both experimental and clinical studies demonstrated that angiotensin II (Ang II) and aldosterone could play a role in the development of insulin resistance, diabetes and cardiovascular diseases. Large randomized clinical trials revealed that blockade of the RAAS with either angiotensin I converting enzyme inhibitors or AT1 receptor blockers results in decreased T2DM incidence, with a minor attenuation of markers for insulin resistance. This review focuses on the role of RAAS in the pathogenesis of insulin resistance, as well as on clinical relevance of RAAS blockade in the prevention and treatment of the metabolic syndrome and pre-diabetes.
MeSH term(s)	Angiotensin II/metabolism ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Animals ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/prevention & control ; Humans ; Insulin Resistance/physiology ; Oxidative Stress/drug effects ; Renin-Angiotensin System/physiology
Chemical Substances	Angiotensin-Converting Enzyme Inhibitors ; Angiotensin II (11128-99-7)
Language	Japanese
Publishing date	2012-09
Publishing country	Japan
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	390903-7
ISSN	0047-1852
ISSN	0047-1852
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Zs.A 429: Show issues

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Article ; Online: Rapid and dramatic glucose-lowering effect of bromocriptine in an inadequately controlled type 2 diabetes patient with prolactinoma.

Igata, Motoyuki / Yagi, Yoshitaka / Hanatani, Satoko / Sakaguchi, Masaji / Ishii, Norio / Yoshinaga, Kayo / Kawashima, Junji / Motoshima, Hiroyuki / Araki, Eiichi

Journal of diabetes investigation

2020 Volume 12, Issue 4, Page(s) 668–671

Abstract: Dopamine receptor agonists are typically used to treat Parkinson's disease and certain pituitary tumors, such as prolactinoma or a growth hormone-producing tumor. A 53-year-old woman with a history of prolactinoma was referred to Kumamoto University ... ...

Abstract	Dopamine receptor agonists are typically used to treat Parkinson's disease and certain pituitary tumors, such as prolactinoma or a growth hormone-producing tumor. A 53-year-old woman with a history of prolactinoma was referred to Kumamoto University Hospital (Kumamoto, Japan) with poorly controlled type 2 diabetes. Her glycated hemoglobin and serum prolactin levels were increased (8.8% and 160.3 ng/mL, respectively). Bromocriptine, a dopamine D
MeSH term(s)	Blood Glucose/drug effects ; Bromocriptine/pharmacology ; Bromocriptine/therapeutic use ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Dopamine Agonists/pharmacology ; Dopamine Agonists/therapeutic use ; Female ; Humans ; Middle Aged ; Prolactinoma/complications ; Prolactinoma/drug therapy
Chemical Substances	Blood Glucose ; Dopamine Agonists ; Bromocriptine (3A64E3G5ZO)
Language	English
Publishing date	2020-08-25
Publishing country	Japan
Document type	Case Reports
ZDB-ID	2625840-7
ISSN	2040-1124 ; 2040-1116
ISSN (online)	2040-1124
ISSN	2040-1116
DOI	10.1111/jdi.13369
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Article ; Online: The Amount of Residual Incretin Regulates the Pancreatic β-cell Function and Glucose Homeostasis.

Kondo, Tatsuya / Kitano, Sayaka / Miyakawa, Nobukazu / Watanabe, Takuro / Goto, Rieko / Sato, Miki / Hanatani, Satoko / Sakaguchi, Masaji / Igata, Motoyuki / Kawashima, Junji / Motoshima, Hiroyuki / Matsumura, Takeshi / Araki, Eiichi

Internal medicine (Tokyo, Japan)

2021 Volume 60, Issue 9, Page(s) 1433–1442

Abstract: The gastrointestinal tract is considered an important endocrine organ for controlling glucose homeostasis via the production of incretins. A 21-year-old man emergently underwent total colectomy due to severe ulcerative colitis, and overt diabetes became ... ...

Abstract	The gastrointestinal tract is considered an important endocrine organ for controlling glucose homeostasis via the production of incretins. A 21-year-old man emergently underwent total colectomy due to severe ulcerative colitis, and overt diabetes became evident. Weekly administration of a glucagon-like peptide (GLP)-1 receptor agonist (RA) dramatically improved his glucose control. Levels of GLP-1 or gastric inhibitory polypeptide (GIP) were low at the baseline in the duodenum and serum of the patient. After 11 months of GLP-1RA treatment, his HbA1c worsened again, and intensive insulin therapy was necessary to control his glucose levels. Our report may explain the significance of residual incretin for maintaining the pancreatic β-cell function.
MeSH term(s)	Adult ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Gastric Inhibitory Polypeptide ; Glucose ; Homeostasis ; Humans ; Incretins ; Insulin ; Male ; Young Adult
Chemical Substances	Blood Glucose ; Incretins ; Insulin ; Gastric Inhibitory Polypeptide (59392-49-3) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-05-01
Publishing country	Japan
Document type	Case Reports ; Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.6026-20
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Article ; Online: Cold adaptation: structural and functional characterizations of psychrophilic and mesophilic acetate kinase.

Tang, Md Abul Kashem / Motoshima, Hiroyuki / Watanabe, Keiichi

The protein journal

2014 Volume 33, Issue 4, Page(s) 313–322

Abstract: Acetate kinase catalyzes the reversible magnesium-dependent phosphoryl transfer from ATP to acetate to form acetyl phosphate and ADP. Here, we report functional and some structural properties of cold-adapted psychrotrophic enzyme; acetate kinase with ... ...

Abstract	Acetate kinase catalyzes the reversible magnesium-dependent phosphoryl transfer from ATP to acetate to form acetyl phosphate and ADP. Here, we report functional and some structural properties of cold-adapted psychrotrophic enzyme; acetate kinase with those from mesophilic counterpart in Escherichia coli K-12. Recombinant acetate kinase from Shewanella sp. AS-11 (SAK) and E. coli K-12 (EAK) were purified to homogeneity following affinity chromatography and followed by Super Q column chromatography as reported before [44]. Both purified enzymes are shared some of the common properties such as (similar molecular mass, amino acid sequence and similar optimum pH), but characterized shift in the apparent optimum temperature of specific activity to lower temperature as well as by a lower thermal stability compared with EAK. The functional comparisons reveal that SAK is a cold adapted enzyme, having a higher affinity to acetate than EAK. In the acetyl phosphate and ADP-forming direction, the catalytic efficiency (k(cat)/K(m)) for acetate was 8.0 times higher for SAK than EAK at 10 °C. The activity ratio of SAK to EAK was increased with decreasing temperature in both of the forward and backward reactions. Furthermore, the activation energy, enthalpy and entropy in both reaction directions that catalyzed by SAK were lower than those catalyzed by EAK. The model structure of SAK showed the significantly reduced numbers of salt bridges and cation-pi interactions as compared with EAK. These results suggest that weakening of intramolecular electrostatic interactions of SAK is involved in a more flexible structure which is likely to be responsible for its cold adaptation.
MeSH term(s)	Acetate Kinase/chemistry ; Acetate Kinase/genetics ; Acetate Kinase/metabolism ; Cold Temperature ; Enzyme Stability ; Escherichia coli ; Kinetics ; Models, Molecular ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Shewanella/enzymology ; Shewanella/genetics ; Shewanella/physiology ; Thermodynamics
Chemical Substances	Recombinant Proteins ; Acetate Kinase (EC 2.7.2.1)
Language	English
Publishing date	2014-05-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2143071-8
ISSN	1875-8355 ; 1572-3887
ISSN (online)	1875-8355
ISSN	1572-3887
DOI	10.1007/s10930-014-9562-1
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Article: Activation of heat shock response improves biomarkers of NAFLD in patients with metabolic diseases.

Kondo, Tatsuya / Miyakawa, Nobukazu / Kitano, Sayaka / Watanabe, Takuro / Goto, Rieko / Suico, Mary Ann / Sato, Miki / Takaki, Yuki / Sakaguchi, Masaji / Igata, Motoyuki / Kawashima, Junji / Motoshima, Hiroyuki / Matsumura, Takeshi / Kai, Hirofumi / Araki, Eiichi

Endocrine connections

2021 Volume 10, Issue 5, Page(s) 521–533

Abstract: Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities but is deteriorated by chronic ... ...

Abstract	Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities but is deteriorated by chronic metabolic insults. Heat shock (HS) with an appropriate mild electrical stimulation (MES) activates HSR and improves metabolic abnormalities including insulin resistance, hyperglycemia and inflammation in metabolic disorders. To analyze the effects of HS + MES treatment on NAFLD biomarkers, three cohorts including healthy men (two times/week, n = 10), patients with metabolic syndrome (four times/week, n = 40), and patients with T2DM (n = 100; four times/week (n = 40) and two, four, seven times/week (n = 20 each)) treated with HS + MES were retrospectively analyzed. The healthy subjects showed no significant alterations in NAFLD biomarkers after the treatment. In patients with metabolic syndrome, many of the NAFLD steatosis markers, including fatty liver index, NAFLD-liver fat score, liver/spleen ratio and hepatic steatosis index and NAFLD fibrosis marker, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improved and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fibrosis score were improved upon the treatment. Thus, HS + MES, a physical intervention, may become a novel treatment strategy for NAFLD as well as metabolic disorders.
Language	English
Publishing date	2021-05-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2668428-7
ISSN	2049-3614
ISSN	2049-3614
DOI	10.1530/EC-21-0084
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Article ; Online: Pioglitazone suppresses macrophage proliferation in apolipoprotein-E deficient mice by activating PPARγ.

Murakami-Nishida, Saiko / Matsumura, Takeshi / Senokuchi, Takafumi / Ishii, Norio / Kinoshita, Hiroyuki / Yamada, Sarie / Morita, Yutaro / Nishida, Shuhei / Motoshima, Hiroyuki / Kondo, Tatsuya / Komohara, Yoshihiro / Araki, Eiichi

Atherosclerosis

2019 Volume 286, Page(s) 30–39

Abstract: Background and aims: Local macrophage proliferation is linked to enhanced atherosclerosis progression. Our previous study found that troglitazone, a thiazolidinedione (TZD), suppressed oxidized low-density lipoprotein (Ox-LDL)-induced macrophage ... ...

Abstract	Background and aims: Local macrophage proliferation is linked to enhanced atherosclerosis progression. Our previous study found that troglitazone, a thiazolidinedione (TZD), suppressed oxidized low-density lipoprotein (Ox-LDL)-induced macrophage proliferation. However, its effects and mechanisms are unclear. Therefore, we investigated the effects of pioglitazone, another TZD, on macrophage proliferation. Methods: Normal chow (NC)- or high-fat diet (HFD)-fed apolipoprotein E-deficient (Apoe Results: Atherosclerosis progression was suppressed in aortic sinuses of pioglitazone-treated Apoe Conclusions: Pioglitazone suppressed macrophage proliferation through PPARγ without inducing macrophage apoptosis. These findings imply that pioglitazone could prevent macrovascular complications in diabetic individuals.
MeSH term(s)	Animals ; Apolipoproteins E/deficiency ; Atherosclerosis/prevention & control ; Cell Proliferation/drug effects ; Macrophages/cytology ; Macrophages/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; PPAR gamma/physiology ; Pioglitazone/pharmacology ; Pioglitazone/therapeutic use
Chemical Substances	Apolipoproteins E ; PPAR gamma ; Pioglitazone (X4OV71U42S)
Language	English
Publishing date	2019-05-03
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2019.04.229
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