|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice显示文摘BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIM To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODS The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTS Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba mice.Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin.In non-diabetic C57 BL/6 J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.CONCLUSION The inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1 D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1 D and its complications. | Lakshini Y Herat Natalie C Ward Aaron L Magno Elizabeth P Rakoczy Marcio G Kiuchi Markus P Schlaich Vance B Matthews | 2020 | World Journal of Gastroenterology2020，26，23： | 3 |
| 2 | Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis显示文摘 | D.Keith George Stefano Goldwurm Graeme A. Macdonald Lex L. Cowley Neal I. Walker Patrick J. Ward Elizabeth C. Jazwinska Lawrie W. Powell | 1998 | Gastroenterology1998，，2： | 2 |
| 3 | Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A‐RIPK1‐dependent necroptosis显示文摘 | Sahar A. Saddoughi Salih Gencer Yuri K. Peterson Katherine E. Ward Archana Mukhopadhyay Joshua Oaks Jacek Bielawski Zdzislaw M. Szulc Raquela J. Thomas Shanmugam P. Selvam Can E. Senkal Elizabeth Garrett‐Mayer Ryan M. De Palma Dzmitry Fedarovich Angen Liu | 2012 | EMBO Mol Med2012，，1： | 2 |
| 4 | The investigation of enhanced bioremediation through the addition of macro and micro nutrients in a PAH contaminated soil显示文摘 | Liebeg Elizabeth Ward Cutright Teresa J | 1999 | International Biodeterioration and Biodegradation1999，44，1： | 1 |
| 5 | The investigation of enhanced bioremediation through the addition of macro and micro nutrients in a PAH contaminated soil显示文摘 | Liebeg Elizabeth Ward Cutright Teresa J | 1999 | International Biodete rioration and Biodegradation1999，44，1： | 1 |
| 6 | Cancer statistics, 2007 显示文摘 | Ahmedin Jemal Rebecca Siegel Elizabeth Ward | 2007 | CA Cancer J Clin2007，57，： | 1 |
| 7 | A Global Profile of Germline Gene Expression in C. elegans显示文摘 | Valerie Reinke Harold E. Smith Jeremy Nance John Wang Carrie Van Doren Rebecca Begley Steven J.M. Jones Elizabeth B. Davis Stewart Scherer Samuel Ward Stuart K. Kim | 2000 | Molecular Cell2000，，3： | 1 |
| 8 | International Variation in Prostate Cancer Incidence and Mortality Rates 显示文摘 | Melissa M. Center Ahmedin Jemal Joannie Lortet-Tieulent Elizabeth Ward Jacques Ferlay Otis Brawley Freddie Bray | 2012 | European Urology2012，，： | 1 |
| 9 | Cancer Statistics 2010 显示文摘 | Ahmedin Jemal Rebecca Siegel Jiaquan Xu and Elizabeth Ward | 2010 | CA Cancer J Clin2010，60，： | 1 |
| 10 | Cancer Statistics, 2009 显示文摘 | Ahmedin Jemal DVM Rebecca Siegel Elizabeth Ward | 2009 | CA : A Cancer Journal for Cliniciarzs2009，55，4： | 1 |
| 11 | Cancer Statistics,2008显示文摘 | Ahmedin Jemal Rebecca Siegel Elizabeth Ward | 2008 | CA Cancer J Clin2008，58，： | 1 |
| 12 | Cancer statistics,2009 显示文摘 | Ahmedin Jemal Rebecca Siegel Elizabeth Ward | 2009 | CA Cancer J Clin2009，59，4： | 1 |
| 13 | Molecular cloning, expression and evaluation of phosphohydrolases for phytate-degrading activity显示文摘 | Elizabeth Moore Veronica R. Helly Orla M. Conneely Pauline P. Ward Ronan F. Power Denis R. Headon | 1995 | Journal of Industrial Microbiology1995，，5： | 1 |
| 14 | Disparities in Receipt of Lymph Node Biopsy Among Early-Stage Female Breast Cancer Patients显示文摘 | Michael T. Halpern Amy Y. Chen Nicole S. Marlow Elizabeth Ward | 2009 | Annals of Surgical Oncology2009，，3： | 1 |
| 15 | Childhood and adolescent cancer statistics, 2014显示文摘 | Elizabeth Ward Carol DeSantis Anthony Robbins Betsy Kohler Ahmedin Jemal | 2014 | CA A Cancer Journal for Clinicians2014，，2： | 1 |
| 16 | Cancer Statistics, 2009 显示文摘 | Ahmedin Jemal Rebecca Siegel Elizabeth Ward | 2009 | CA Cancer J Clin2009，59，4： | 1 |
| 17 | Cancer statistics, 2009显示文摘 | Ahmedin Jemal Rebecca Siegel Elizabeth Ward | 2009 | CA Cancer J Clin2009，59，4： | 1 |
| 18 | Cancer statistics,2007显示文摘 | Ahmedin Jemal Rebecca Siegel Elizabeth ward | 2007 | CA Cancer Joural of Clinical2007，57，1： | 1 |
| 19 | Cancer Sttistics显示文摘 | Jemal Ahmedin Murray Taylor Ward Elizabeth | 2005 | CA Cancer J Lin2005，55，： | 1 |
| 20 | Cancer Statistics, 2007 显示文摘 | Ahmedin Jemal Rebecca Siegel Elizabeth Ward | 2007 | CA Cancer Joural of Clinical2007，57，1： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员