研究等業績 - 原著論文 - 藤田 浩樹
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Sasaki K.
Biochemical and Biophysical Research Communications ( Biochemical and Biophysical Research Communications ) 741 151016 - 151016 2024年12月 [査読有り]
研究論文（学術雑誌） 国内共著
The physiological actions of a gut hormone, glucagon-like peptide-1 (GLP-1), in Alzheimer's disease (AD) brain remain poorly understood, although GLP-1 receptor (GLP-1R) expression in this organ has been shown in several experimental studies. Therefore, we explored whether the GLP-1R signaling promotes the clearance of amyloid β (Aβ) (1-42) which is a core pathological hallmark of AD, focusing on the water channel protein aquaporin 4 (AQP4) localized to astrocyte endfeet perivascular membranes in intact brain. First, we confirmed that Glp1r mRNA is predominantly expressed at perivascular site of astrocytes in normal mouse cerebral cortex through in situ hybridization analysis. Next, we observed that 20-week subcutaneous administration of a GLP-1R agonist (GLP-1RA) liraglutide significantly reduced Aβ (1-42) accumulation in the cerebral cortex and improved spatial working memory in an AD mouse model, AppNL-G-F/NL-G-F mice. Furthermore, our current data revealed that the 4-week liraglutide treatment relocalized subcellular AQP4 in morphologically injured reactive astrocytes of AppNL-G-F/NL-G-F mice to the cell surface perivascular site through PKA-mediated AQP4 phosphorylation. Such translocation of phosphorylated AQP4 to astrocyte cell surface following incubation with liraglutide was observed also in the present in vitro study using the cell line in which AQP4 cDNA was introduced into immortalized human astrocyte. These results suggest that enhanced intracerebral GLP-1R signaling following peripheral administration of GLP-1RA restores AQP4 subcellular polarization in reactive astrocytes and would promote Aβ excretion possibly through increasing AQP4-mediated intracerebral water flux in the brain in AD.
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Sugimoto T.
Journal of Prevention of Alzheimer's Disease ( Journal of Prevention of Alzheimer's Disease ) 11 ( 6 ) 1604 - 1614 2024年12月 [査読有り]
研究論文（学術雑誌） 国内共著
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Recurrent nocturnal hypoglycemic hemiplegia: a case report and review of the literature
Toyama H.
Endocrine Journal ( Endocrine Journal ) 71 ( 4 ) 409 - 416 2024年 [査読有り]
研究論文（学術雑誌） 国内共著
A 67-year-old man with type 1 diabetes, Cronkhite-Canada syndrome, and membranous nephropathy who received insulin therapy was admitted to our hospital with right hemiplegia and dysarthria. Brain magnetic resonance imaging revealed a lesion with a high diffusion-weighted imaging signal and low apparent diffusion coefficient signal in the posterior limb of the left internal capsule. He was hypoglycemic with a blood glucose level of 56 mg/dL (3.1 mmol/L). Following glucose administration, the patient's symptoms resolved within several hours. The patient experienced similar transient hypoglycemic hemiplegia at midnight, three times within 10 days. In a literature review of 170 cases of hypoglycemic hemiplegia, 26 cases of recurrent hemiplegia were investigated. Recurrent hypoglycemic hemiplegia occurs more frequently on the right side than on the left side, and most recurrences occur within approximately a week, almost exclusively at midnight and in the early morning. We speculate that hypoglycemia-associated autonomic failure may be involved in the nocturnal recurrence of episodes. In our patient, depleted endogenous insulin secretion and lipodystrophy at the injection site, may have acted as additional factors, leading to severe hypoglycemia despite the absence of apparent autonomic neuropathy. Clinically, it is important to recognize hypoglycemia as a cause of hemiplegia to avoid unnecessary intervention and to maintain an appropriate blood glucose level at midnight and early in the morning to prevent recurrent hypoglycemic hemiplegia.
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Takahashi Y.
Journal of Cachexia, Sarcopenia and Muscle ( Journal of Cachexia, Sarcopenia and Muscle ) 14 ( 6 ) 2703 - 2718 2023年12月 [査読有り]
研究論文（学術雑誌） 国内共著
BACKGROUND: Intramuscular adipose tissue (IMAT) formation derived from muscle fibro-adipogenic progenitors (FAPs) has been recognized as a pathological feature of sarcopenia. This study aimed to explore whether genetic and pharmacological gastric inhibitory polypeptide (GIP) receptor antagonism suppresses IMAT accumulation and ameliorates sarcopenia in mice. METHODS: Whole body composition, grip strength, skeletal muscle weight, tibialis anterior (TA) muscle fibre cross-sectional area (CSA) and TA muscle IMAT area were measured in young and aged male C57BL/6 strain GIP receptor (Gipr)-knockout (Gipr-/- ) and wild-type (Gipr+/+ ) mice. FAPs isolated from lower limb muscles of 12-week-old Gipr+/+ mice were cultured with GIP, and their differentiation into mature adipocytes was examined. Furthermore, TA muscle IMAT area and fibre CSA were measured in untreated Gipr-/- mice and GIP receptor antagonist-treated Gipr+/+ mice after glycerol injection into the TA muscles. RESULTS: Body composition analysis revealed that 104-week-old Gipr-/- mice had a greater proportion of lean tissue mass (73.7 ± 1.2% vs. 66.5 ± 2.7%, P < 0.05 vs. 104-week-old Gipr+/+ mice) and less adipose tissue mass (13.1 ± 1.3% vs. 19.4 ± 2.6%, P < 0.05 vs. 104-week-old Gipr+/+ mice). Eighty-four-week-old Gipr-/- mice exhibited increases in grip strength (P < 0.05), weights of TA (P < 0.05), soleus (P < 0.01), gastrocnemius (P < 0.05) and quadriceps femoris (P < 0.01) muscles, and average TA muscle fibre CSA (P < 0.05) along with a reduction in TA muscle IMAT area assessed by the number of perilipin-positive cells (P < 0.0001) compared with 84-week-old Gipr+/+ mice. Oil Red O staining analysis revealed 1.6- and 1.7-fold increased adipogenesis in muscle FAPs cultured with 10 and 100 nM of GIP (P < 0.01 and P < 0.001 vs. 0 nM of GIP, respectively). Furthermore, both untreated Gipr-/- mice and GIP receptor antagonist-treated Gipr+/+ mice for 14 days after glycerol injection into the TA muscles at 12 weeks of age showed reduced TA muscle IMAT area (1.39 ± 0.38% and 2.65 ± 0.36% vs. 6.54 ± 1.30%, P < 0.001 and P < 0.01 vs. untreated Gipr+/+ mice, respectively) and increased average TA muscle fibre CSA (P < 0.01 and P < 0.05 vs. untreated Gipr+/+ mice, respectively). CONCLUSIONS: GIP promotes the differentiation of muscle FAPs into adipocytes and its receptor antagonism suppresses IMAT accumulation and promotes muscle regeneration. Pharmacological GIP receptor antagonism may serve as a novel therapeutic approach for sarcopenia.
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Efficacy and Safety of 6-Month High Dietary Protein Intake in Hospitalized Adults Aged 75 or Older at Nutritional Risk: An Exploratory, Randomized, Controlled Study
Shota Moyama, Yuichiro Yamada, Noboru Makabe, Hiroki Fujita, Atsushi Araki, Atsushi Suzuki, Yusuke Seino, Kenichiro Shide, Kyoko Kimura, Kenta Murotani, Hiroto Honda, Mariko Kobayashi, Satoshi Fujita, Koichiro Yasuda, Akira Kuroe, Katsushi Tsukiyama, Yutaka Seino, Daisuke Yabe
Nutrients 2023年04月 [査読有り]
研究論文（学術雑誌） 国内共著
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Relationships among Postprandial Plasma Active GLP-1 and GIP Excursions, Skeletal Muscle Mass, and Body Fat Mass in Patients with Type 2 Diabetes Treated with Either Miglitol, Sitagliptin, or Their Combination: A Secondary Analysis of the MASTER Study.
Masahiro Sato, Hiroki Fujita, Hiroki Yokoyama, Atsushi Mikada, Yohei Horikawa, Yuya Takahashi, Yuichiro Yamada, Hironori Waki, Takuma Narita
Journal of clinical medicine 12 ( 9 ) 2023年04月 [査読有り]
研究論文（学術雑誌）
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Fujita H.
Biochemical and Biophysical Research Communications ( Biochemical and Biophysical Research Communications ) 635 84 - 91 2022年12月 [査読有り]
研究論文（学術雑誌） 国内共著
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Kato S.
Diabetology International ( Diabetology International ) 13 ( 4 ) 698 - 703 2022年10月 [査読有り]
研究論文（学術雑誌） 国内共著
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Takahashi K.
Diabetes Therapy ( Diabetes Therapy ) 13 ( 7 ) 1383 - 1393 2022年07月 [査読有り]
研究論文（学術雑誌） 国内共著
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Pick the best of both glucose and lipid metabolism
Tatsunori Shimizu, Yuya Takahashi, Hiroki Fujita, Hironori Waki
Journal of Diabetes Investigation ( Wiley ) 13 ( 7 ) 1132 - 1133 2022年07月 [査読有り] [招待有り]
研究論文（学術雑誌） 国内共著
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Effects of GLP-1 receptor agonist on changes in the gut bacterium and the underlying mechanisms
Kato S.
Scientific Reports ( Scientific Reports ) 11 ( 1 ) 2021年12月 [査読有り]
研究論文（学術雑誌） 国内共著
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Sugimoto T.
Frontiers in Aging Neuroscience ( Frontiers in Aging Neuroscience ) 13 2021年07月 [査読有り]
研究論文（学術雑誌） 国内共著
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Takahashi Y.
International Journal of Molecular Sciences ( International Journal of Molecular Sciences ) 22 ( 11 ) 2021年06月 [査読有り]
研究論文（学術雑誌） 国内共著
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Sato T.
Endocrinology (United States) ( Endocrinology (United States) ) 161 ( 12 ) 2020年12月 [査読有り]
研究論文（学術雑誌）
<jats:title>Abstract</jats:title>
<jats:p>A number of disease states, including type 2 diabetes (T2D), are associated with an increased risk of pulmonary infection. Glucagon-like peptide-1 (GLP-1) receptor agonists are used to treat T2D and exert anti-inflammatory actions through a single, well-defined GLP-1 receptor (GLP-1R). Although highly expressed in the lung, little is known about the role of the GLP-1R in the context of pulmonary inflammation. Here we examined the consequences of gain or loss of GLP-1R activity in infectious and noninfectious lung inflammation. We studied wild-type mice treated with a GLP-1R agonist, and Glp1r–/– mice, in the setting of bleomycin-induced noninfectious lung injury and influenza virus infection. Loss of the GLP-1R attenuated the severity of bleomycin-induced lung injury, whereas activation of GLP-1R signaling increased pulmonary inflammation via the sympathetic nervous system. In contrast, GLP-1R agonism reduced the pathogen load in mice with experimental influenza virus infection in association with increased expression of intracellular interferon-inducible GTPases. Notably, the GLP-1 receptor agonist liraglutide improved the survival rate after influenza virus infection. Our results reveal context-dependent roles for the GLP-1 system in the response to lung injury. Notably, the therapeutic response of GLP-1R agonism in the setting of experimental influenza virus infection may have relevance for ongoing studies of GLP-1R agonism in people with T2D susceptible to viral lung injury.</jats:p> -
Otomo H.
Metabolism: Clinical and Experimental ( Metabolism: Clinical and Experimental ) 113 2020年12月 [査読有り]
研究論文（学術雑誌） 国内共著
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Suganuma Y.
Journal of Diabetes Investigation ( Journal of Diabetes Investigation ) 11 ( 2 ) 389 - 399 2020年03月 [査読有り]
研究論文（学術雑誌）
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Inhibition of GIP signaling extends lifespan without caloric restriction
Hoizumi M.
Biochemical and Biophysical Research Communications ( Biochemical and Biophysical Research Communications ) 513 ( 4 ) 974 - 982 2019年06月 [査読有り]
研究論文（学術雑誌）
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Fukuoka Y.
Journal of Diabetes Investigation ( Journal of Diabetes Investigation ) 10 ( 2 ) 322 - 330 2019年03月 [査読有り]
研究論文（学術雑誌）
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COMPARISON OF WESTERN BLOT ANALYSES IN NATIVE AND ACID-ETHANOL-EXTRACTED SERUM FOR DETECTING BIG IGF-II IN PATIENTS WITH NON-ISLET CELL TUMOR HYPOGLYCEMIA
Riko Kashima, Hiroki Fujita, Hitomi Otomo, Yuki Fukuoka, Yuichiro Yamada
Akita J Med 45 45 - 50 2018年12月 [査読有り]
研究論文（学術雑誌）
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SIRT3 deficiency leads to induction of abnormal glycolysis in diabetic kidney with fibrosis
Srivastava S.P.
Cell Death and Disease ( Cell Death and Disease ) 9 ( 10 ) 2018年10月 [査読有り]
研究論文（学術雑誌）
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Food intake affects sperm-egg fusion through the GIP/PSG17 axis in mice
Shimizu T.
Endocrinology ( Endocrinology ) 158 ( 7 ) 2134 - 2144 2017年07月 [査読有り]
研究論文（学術雑誌）
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Stromal cell-derived factor-1 is upregulated by dipeptidyl peptidase-4 inhibition and has protective roles in progressive diabetic nephropathy
Takashima S, Fujita H, Fujishima H, et al.
Kidney International 90 ( 4 ) 783 - 796 2016年10月 [査読有り]
研究論文（学術雑誌） 単著
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Poorly-controlled Acromegaly Accompanied by Subclinical Adrenal Cushing’s Syndromu after Surgery for Multiple Endocrine Tumors
Ishikawa M, Kato M, Sasaki H, Morii T, Fujita H, Katei M, Narita T, Yamada Y
Intern Med 54 ( 6 ) 617 - 620 2015年10月 [査読有り]
研究論文（学術雑誌） 単著
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DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria via up-regulation of SDF-1α in type 2 diabetic patients with incipient nephropathy
Fujita H, Taniai H, Murayama H, Ohshiro H, Hayashi H, Sato S, Kikuchi N, Komatsu T, Komatsu K, Komatsu K, Narita T, Yamada Y
Endocr J 61 ( 2 ) 159 - 166 2014年10月 [査読有り]
研究論文（学術雑誌）
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The protective roles of GLP-1R signaling in diabetic nephropathy: possible mechanism and therapeutic potential
Fujita H, Morii T, Fujishima H, Sato T, Shimizu T, Hosoba M, Tsukiyama K, Narita T, Takahashi T, Drucker DJ, Seino Y, Yamada Y
Kidney Int 85 ( 3 ) 579 - 589 2014年03月 [査読有り]
研究論文（学術雑誌）
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Assessment of renal function in ,ice with unilateral ureteral obstruction using 99mTc-MAG3 dynamic scintigraphy
Tantawy MN, Jiang R, Wang F, Takahashi K, Peterson TE, Zemel D, Hao CM, Fujita H, Harris RC, Quarles CC, Takahashi T
BMC Nephrol 13 168 2012年12月 [査読有り]
研究論文（学術雑誌）
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SOD1,but not SOD3,deficiency accelerates diabetic renal injury in C57BL/6-Ins2(Akita)diabeticmice
Fujita H, Fujishima H, Takahashi K, Sato T, Shimizu T, Morii T, Shimizu T,
METABOLISM CLINICAL AND EXPERIMENTAL 61 1714 - 1724 2012年12月 [査読有り]
研究論文（学術雑誌）
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Generation of a Conditional Allele for the Mouse Endothelial Nitric Oxide Synthase Gene
Jiang R, Wang S, K Takahashi, Fujita H, Fruci RC, Breyer DM, Harris CR, and T Takahashi
genesis 50 ( 9 ) 685 - 692 2012年09月 [査読有り]
研究論文（学術雑誌）
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Comparisons of the effects of 12-week administration of miglitol and voglibose on the responses of plasma incretins after a mixed meal in Japanese type 2 diabetic patients
Narita T, Yokoyama H, Yamashita R, Sato T, Hosoba M, Morii T, Fujita H, Tsukiyama K, Yamada Y
Diabetes Obes Metab 14 ( 3 ) 283 - 287 2012年03月 [査読有り]
研究論文（学術雑誌）
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Modulation of renal superoxide dismutase by telmisartan therapy in C57BL/6-Ins2(Akita) diabetic mice
Fujita H, Fujishima H, Morii T, Sakamoto T, Komatsu K, Hosoba M, Narita T, Takahashi K, Takahashi T, Yamada Y
Hypertens Res 14 ( 3 ) 283 - 287 2012年02月 [査読有り]
研究論文（学術雑誌）
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Reduction of circulating superoxide dismutase activity in type 2 diabetic patients with microalbuminuria and its modulation by telmisartan therapy
Fujita H, Sakamoto T, Komatsu K, Fujishima H, Morii T, Narita T, Takahashi T, Yamada Y
Hypertens Res 4 1302 - 1308 2011年11月 [査読有り]
研究論文（学術雑誌）
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Efficacy and safety of patient-directed titration of once-daily pre-dinner premixed biphasic insulin aspart 70/30 injection in Japanese type 2 diabetic parients with oral antisiabetic drug failure: STEP-AKITA study
Narita T, Goto T, Suganuma Y, Hosoba M, Morii T, Sato T, Fujita H, Miura T, Shimotomai T, Yamada Y, Kakei M
J Diabet Invest 2 63 - 70 2011年02月 [査読有り]
研究論文（学術雑誌）