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Improved <i>β</i>-cell function rather than increased insulin sensitivity is associated with reduction in hemoglobin A1c in newly diagnosed Type 2 diabetic patients treated with metformin

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Journal of Diabetes Mellitus 2014年第1期4卷 44-49页

作者： Satoru Sumitani shinya Morita Reiko Deguchi Koichi Hirai Kosuke Mukai Yoshihiko Utsu Shunji Miki Bunzo Sato Hideji nakamura Soji Kasayama Center for Preventive Medicine Nissay Hospital Osaka Japan Department of Medicine Nissay Hospital Osaka Japan

β-cell dysfunction and decreased insulin sensitivity are believed to be two chief mechanisms that participate in deterioration of glycemic control in Type 2 diabetes. Meformin is widely accepted as the first-line oral agent in the treatment of Type 2 diabetes. However, the relative contributions of improved β-cell function and increased insulin sensitivity to reduction in hemoglobin A1c (HbA1c) are unclear in newly diagnosed Type 2 diabetic patients treated with metformin. We investigated β-cell function and insulin sensitivity in relation to reduction in HbA1c in 20 newly diagnosed Type 2 diabetic patients (17 men and 3 women, mean age 49.1 ± 10.1 years, mean body mass index 26.4 ± 5.2 kg/m2) treated with metformin for 16 weeks. We used homeostasis model assessment (HOMA) 2%B and HOMA2%S as estimates of β-cell function and insulin sensitivity, respectively. Median HOMA2%B and HOMA2%S significantly increased from 38.8 to 68.8 (p p = 0.004), respectively. In univariate regression analysis, reduction in HbA1c was highly correlated with change in HOMA2%B (r = -0.866, p < 0.001), but not with that in HOMA2%S (r = -0.264, p = 0.260). Furthermore, multivariate regression analysis with reduction in HbA1c as a dependent variable showed that increase in HOMA2%B but not that in HOMA2%S was a significant dependent variable (β = -0.847, p β-cell function rather than increased insulin sensitivity is associated with reduction in HbA1c. These results suggest that metformin reduces HbA1c chiefly through improved β-cell function rather than increased insulin sensitivity in patients with newly diagnosed Type 2 diabetes.

关键词： Metformin Type 2 Diabetes β-Cell Function Insulin Sensitivity

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Bcr-Abl-mediated Raf kinase inhibitor protein suppression promotes chronic myeloid leukemia progenitor cells proliferation

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Stem Cell Discovery 2011年第3期1卷 54-66页

作者： Satoki nakamura Tomohiro Yagyu Tomonari Takemura Lin Tan Yasuyuki Nagata Daisuke Yokota Isao Hirano Kiyoshi Shibata Michio Fujie shinya Fujisawa Kazunori Ohnishi 不详

The Ras/Raf-1/MEK/ERK pathway is constitutively activated in Bcr-Abl transformed cells, and Ras activity enhances the oncogenic ability of Bcr-Abl. On the hand, Raf kinase inhibitor protein (RKIP) inhibits activation of MEK by Raf-1 and its downstream signal transduction, resulting in blocking the MAP kinase pathway. Moreover, Raf-1 has been reported to regulate cell cycle progression. However, the mechanism by which Bcr-Abl promotes the cell cycle progression through Raf-1 is not completely understood. In the present study, we found that the expression of RKIP was suppressed in CML cells, and investigated the interaction between RKIP and Bcr-Abl in CML cells. In aldehyde dehydrogenase (ALDH)hi/CD34+ cells derived from CML patients, the inhibition of Bcr-Abl induced RKIP expression and reduced the phosphorylated-FOXM1 (pFOXM1) status, resulting in inhibited colony formation of Bcr-Abl+ progenitor cells. Moreover, overexpression of RKIP significantly decreased the colony numbers, reduced the pFOXM1 status, and reduced pFOXM-1 target genes such as Skp2, Cdc25B and KIS, and induced the expression of p27Kip1a and p21Cip1. Thus, Bcr-Abl represses the expression of RKIP, and continuously activates FOXM1, resulting in the proliferation of CML progenitor cells through the cell cycle modulation.

关键词： RKIP FOXM1 Bcr-Abl Progenitor cells Cell cycle

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Usefulness of vonoprazan,a potassium ion-competitive acid blocker,for primary eradication of Helicobacter pylori

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2016年第4期7卷 550-555页

作者： shinya Yamada Takumi Kawakami Yoshikazu Nakatsugawa Takahiro Suzuki Hideki Fujii Naoya Tomatsuri Hideki nakamura Hideki Sato Yusuke Okuyama Hiroyuki Kimura Norimasa Yoshida Department of Gastroenterology Japanese Red Cross Kyoto Daiichi Hospital

AIM To investigate usefulness of triple therapy with vonoprazan,a potassium ion-competitive acid blocker and antibiotics,for Helicobacter pylori(***) *** The *** eradication rate was examined in 2507 patients(2055 undergoing primary eradication and 452 undergoing secondary eradication,excluding patients with subtotal gastrectomy) at the Japanese Red Cross Kyoto Daiichi Hospital from March 2013 to September *** patients treated from March 2013 to February 2015,a proton pump inhibitor(PPI) was used to reduce acid secretion,while vonoprazan was used after March *** success rates of the 2 regimens(PPI + amoxicillin + clarithromycin/metronidazole,or vonoprazan + amoxicillin + clarithromycin/metronidazole) were *** The success rate of primary *** eradication was significantly higher in the vonoprazan *** stratified by the underlying disease,a significant increase of the *** eradication rate was observed in patients with chronic gastritis.A significantly lower *** eradication rate was observed in younger patients compared to older patients in the PPI group,but there was no difference according to age in the vonoprazan *** the otherhand,the success rate of secondary eradication was similar at approximately 90% in both *** Vonoprazan is very useful for primary eradication of ***,and may become a first-line acid secretion inhibitor instead of PPIs.

关键词： Helicobacter pylori Eradication Vonoprazan Chronic gastritis Potassium ion-competitive acid blocker

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Therapeutic efficacy of ramucirumab after lenvatinib for post-progression treatment of unresectable hepatocellular carcinoma

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Gastroenterology Report 2021年第2期9卷 133-138,I0002页

作者： Atsushi Hiraoka Takashi Kumada Toshifumi Tada Chikara Ogawa Joji Tani shinya Fukunishi Masanori Atsukawa Masashi Hirooka Kunihiko Tsuji Toru Ishikawa Koichi Takaguchi Kazuya Kariyama Ei Itobayashi Kazuto Tajiri Noritomo Shimada Hiroshi Shibata Hironori Ochi Kazuhito Kawata Hidenori Toyoda Hideko Ohama Kazuhiro Nouso Akemi Tsutsui Takuya Nagano Norio Itokawa Korenobu Hayama Taeang Arai Michitaka Imai Yohei Koizumi Shinichiro nakamura Kojiro Michitaka Yoichi Hiasa Masatoshi Kudo Gastroenterology Center Ehime Prefectural Central HospitalEhimeJapan Department of Gastroenterology and Hepatology Ogaki Municipal HospitalGifuJapan Department of Internal Medicine Himeji Red Cross HospitalHyogoJapan Department of Gastroenterology and Hepatology Takamatsu Red Cross HospitalTakamatsuJapan Department of Gastroenterology and Hepatology Kagawa universityKagawaJapan Department of Gastroenterology Osaka Medical CollegeOsakaJapan Division of Gastroenterology and Hepatology Department of Internal MedicineNippon Medical SchoolTokyoJapan Department of Gastroenterology and Metabology Ehime University Graduate School of MedicineEhimeJapan Center of Gastroenterology Teine Keijinkai HospitalSapporoJapan Department of Gastroenterology Saiseikai Niigata HospitalNiigataJapan Department of Hepatology Kagawa Prefectural Central HospitalTakamatsuJapan Department of Gastroenterology Okayama City HospitalOkayamaJapan Department of Gastroenterology Asahi General HospitalAsahiJapan Department of Gastroenterology Toyama University HospitalToyamaJapan Division of Gastroenterology and Hepatology Otakanomori HospitalKashiwaJapan Department of Gastroenterology Tokushima Prefectural Central HospitalTokushimaJapan Hepato-biliary Center Matsuyama Red Cross HospitalMatsuyamaJapan Department of Hepatology Hamamatsu University School of MedicineHamamatsuJapan Department of Gastroenterology Kindai UniversityOsakaJapan

Background:Lenvatinib is used for unresectable hepatocellular carcinoma(u-HCC)as first-line,as well as second-and third-line therapy in *** evaluated the therapeutic efficacy of newly developed ramucirumab when given after lenvatinib for post-progression ***:Of 385 patients with u-HCC and treated with lenvatinib at 16 different institutions in Japan between May 2018 and January 2020,28 who received ramucirumab as the next treatment were enrolled and therapeutic responses were evaluated in a retrospective ***:The median age of the 28 patients given ramucirumab was 70 years and the median albumin-bilirubin score *** the 28 patients,23 were male,21 were classified as Child-Pugh A and 7 as Child-Pugh B,and 25 were Barcelona Clinic Liver Cancer Stage *** was given as second-line therapy in 14,third-line in 9,and fourth-line in *** response was obtained in only 26 patients;the objective response rate was 3.8%(1/26)and the disease-control rate was 42.3%(11/26),with a median period to progression of 2.0 *** reasons for discontinuation of ramucirumab were progression of disease in 16 and Grade 3 adverse events(gastrointestinal bleeding,ascites)in ***:The anticipated therapeutic efficacy of ramucirumab for post-progression treatment following lenvatinib was not seen in our early experience.

关键词： hepatocellular carcinoma ramucirumab lenvatinib sorafenib

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