Research Achievements - Original paper -

Multidomain Intervention Trial for Preventing Cognitive Decline among Older Adults with Type 2 Diabetes: J-MIND-Diabetes

Sugimoto T.

Journal of Prevention of Alzheimer's Disease ( Journal of Prevention of Alzheimer's Disease )  11 ( 6 ) 1604 - 1614   2024.12  [Refereed]

Research paper (journal)   Domestic Co-author

DOI

Gastric inhibitory polypeptide receptor antagonism suppresses intramuscular adipose tissue accumulation and ameliorates sarcopenia

Takahashi Y.

Journal of Cachexia, Sarcopenia and Muscle ( Journal of Cachexia, Sarcopenia and Muscle )  14 ( 6 ) 2703 - 2718   2023.12  [Refereed]

Research paper (journal)   Domestic Co-author

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.

DOI PubMed

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     2023.04  [Refereed]

Research paper (journal)   Domestic Co-author

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 )   2023.04  [Refereed]

Research paper (journal)  

DOI PubMed

Dual inhibition of SGLT2 and DPP-4 promotes natriuresis and improves glomerular hemodynamic abnormalities in KK/Ta-Ins2^Akita mice with progressive diabetic kidney disease

Fujita H.

Biochemical and Biophysical Research Communications ( Biochemical and Biophysical Research Communications )  635   84 - 91   2022.12  [Refereed]

Research paper (journal)   Domestic Co-author

DOI

Cases of fulminant type 1 and type 2 diabetes mellitus whose HbA1c levels were unmeasurable due to increased labile HbA1c

Kato S.

Diabetology International ( Diabetology International )  13 ( 4 ) 698 - 703   2022.10  [Refereed]

Research paper (journal)   Domestic Co-author

DOI

A Pilot Study to Assess Glucose, Insulin, and Incretin Responses Following Novel High Resistant Starch Rice Ingestion in Healthy Men

Takahashi K.

Diabetes Therapy ( Diabetes Therapy )  13 ( 7 ) 1383 - 1393   2022.07  [Refereed]

Research paper (journal)   Domestic Co-author

DOI

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   2022.07  [Refereed]  [Invited]

Research paper (journal)   Domestic Co-author

DOI PubMed

Effects of GLP-1 receptor agonist on changes in the gut bacterium and the underlying mechanisms

Kato S.

Scientific Reports ( Scientific Reports )  11 ( 1 )   2021.12  [Refereed]

Research paper (journal)   Domestic Co-author

DOI

The Multi-Domain Intervention Trial in Older Adults With Diabetes Mellitus for Prevention of Dementia in Japan: Study Protocol for a Multi-Center, Randomized, 18-Month Controlled Trial

Sugimoto T.

Frontiers in Aging Neuroscience ( Frontiers in Aging Neuroscience )  13   2021.07  [Refereed]

Research paper (journal)   Domestic Co-author

DOI

Reduction of superoxide dismutase 1 delays regeneration of cardiotoxin-injured skeletal muscle in kk/ta-ins2^akita mice with progressive diabetic nephropathy

Takahashi Y.

International Journal of Molecular Sciences ( International Journal of Molecular Sciences )  22 ( 11 )   2021.06  [Refereed]

Research paper (journal)   Domestic Co-author

DOI

GLP-1 Receptor Signaling Differentially Modifies the Outcomes of Sterile vs Viral Pulmonary Inflammation in Male Mice

Sato T.

Endocrinology (United States) ( Endocrinology (United States) )  161 ( 12 )   2020.12  [Refereed]

Research paper (journal)  

<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>

DOI CiNii Research

Sodium-glucose cotransporter 2 inhibition attenuates protein overload in renal proximal tubule via suppression of megalin O-GlcNacylation in progressive diabetic nephropathy

Otomo H.

Metabolism: Clinical and Experimental ( Metabolism: Clinical and Experimental )  113   2020.12  [Refereed]

Research paper (journal)   Domestic Co-author

DOI

Magnitude of slowing gastric emptying by glucagon-like peptide-1 receptor agonists determines the amelioration of postprandial glucose excursion in Japanese patients with type 2 diabetes

Suganuma Y.

Journal of Diabetes Investigation ( Journal of Diabetes Investigation )  11 ( 2 ) 389 - 399   2020.03  [Refereed]

Research paper (journal)  

DOI CiNii Research

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   2019.06  [Refereed]

Research paper (journal)  

DOI

Importance of physical evaluation using skeletal muscle mass index and body fat percentage to prevent sarcopenia in elderly Japanese diabetes patients

Fukuoka Y.

Journal of Diabetes Investigation ( Journal of Diabetes Investigation )  10 ( 2 ) 322 - 330   2019.03  [Refereed]

Research paper (journal)  

DOI

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   2018.12  [Refereed]

Research paper (journal)  

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 )   2018.10  [Refereed]

Research paper (journal)  

DOI

Food intake affects sperm-egg fusion through the GIP/PSG17 axis in mice

Shimizu T.

Endocrinology ( Endocrinology )  158 ( 7 ) 2134 - 2144   2017.07  [Refereed]

Research paper (journal)  

DOI

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   2016.10  [Refereed]

Research paper (journal)   Single author

DOI

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   2015.10  [Refereed]

Research paper (journal)   Single author

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   2014.10  [Refereed]

Research paper (journal)  

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   2014.03  [Refereed]

Research paper (journal)  

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   2012.12  [Refereed]

Research paper (journal)  

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   2012.12  [Refereed]

Research paper (journal)  

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   2012.09  [Refereed]

Research paper (journal)  

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   2012.03  [Refereed]

Research paper (journal)  

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   2012.02  [Refereed]

Research paper (journal)  

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   2011.11  [Refereed]

Research paper (journal)  

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   2011.02  [Refereed]

Research paper (journal)