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| 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 | Laryngeal and oropharyngeal cancer, and alcohol dehydrogenase 3 and glutathione S-transferase M1 polymorphisms显示文摘 | Coutelle C Ward PJ Fleury B Quattrocchi P Chambrin H Iron A | 1997 | Hum Genet1997，99，3： | 3 |
| 3 | Factors affecting recovery and quality of oocytes for bovine embryo production in vitro using ovum pick-up technology显示文摘 | Ward F A Lonergan P Enright B P | 2000 | Theriogenology2000，54，： | 2 |
| 4 | Influence of flourprotein,extraction rate,particle size,and starch damage on the quality characteristics of dry noodle显示文摘 | OH N H SEIB P A WARD A B | 1985 | Cereal Chem1985，62，： | 1 |
| 5 | Phaseshift time-stepping for reverse-time migration 显示文摘 | Wards B D Margrave G F Lamoureux M P | 2008 | Expanded Abstracts of 78^th Annual Internat SEG Mtg2008，，： | 1 |
| 6 | A central role of salicylic acid in plant disease resistance显示文摘 | DELANEY T P UKNES S VERNOOIJ B FRIEDRICH L WER- MANN K NEGROTYO D GAFFNEY T GUT-RELLA M KESS- MANN H WARD E RYALS J | 1994 | Science1994，266，5188： | 1 |
| 7 | Current and future horizons in laryngeal and voice research显示文摘 | Ward P H Hanson D G Gerratt B R | 1989 | Ann Otol Rhinol Laryngol1989，98，2： | 1 |
| 8 | Effects of in- travenous dexmedetomidine in humans, Ⅱ : hemodynamic changes 显示文摘 | BLOOR B C WARD D S BELLEVILLE J P | 1992 | Anesthesiology1992，77，6： | 1 |
| 9 | The properties of PIPD-fiber/epoxy composites显示文摘 | BREW B HINE P J WARD I M | 1999 | Composites Science and Technology1999，59，： | 1 |
| 10 | The major genetic determinants of HIV-1control affect HLA class I peptide presentation显示文摘 | International HIV Controllers Study Pereyra F Jia X McLaren P J Telenti A de Bakker P I Walker B D Ripke S Brumme C J Pulit S L Carrington M Kadie C M Carlson J M Heckerman D Graham R R Plenge R M Deeks S G Gianniny L Crawford G Sullivan J Gonzalez E Davies L Camargo A Moore JM Beattie N Gupta S Crenshaw A Burtt N P Guiducci C Gupta N Gao X Qi Y Yuki Y Piechocka-Trocha A Cutrell E Rosenberg R Moss K L Lemay P O'Leary J Schaefer T Verma P Toth I Block B Baker B Rothchild A Lian J Proudfoot J Alvino D M Vine S Addo M M Allen T M Altfeld M Henn M R Le Gall S Streeck H Haas D W Kuritzkes D R Robbins G K Shafer R W Gulick R M Shikuma C M Haubrich R Riddler S Sax P E Daar E S Ribaudo H J Agan B Agarwal S Ahern R L Allen B L Altidor S Altschuler E L Ambardar S Anastos K Anderson B Anderson V Andrady U Antoniskis D Bangsberg D Barbaro D Barrie W Bartczak J Barton S Basden P Basgoz N Bazner S Bellos N C Benson A M Berger J Bernard N F Bernard A M Birch C Bodner S J Bolan R K Boudreaux E T Bradley M Braun J F Brndjar J E Brown S J Brown K Brown S T Burack J Bush LM Cafaro V Campbell O Campbell J Carlson R H Carmichael J K Casey K K Cavacuiti C Celestin G Chambers S T Chez N Chirch L M Cimoch P J Cohen D Cohn LE Conway B Cooper D A Cornelson B Cox D T Cristofano M V Cuchural G Jr Czartoski J L Dahman J M Daly J S Davis B T Davis K Davod S M DeJesus E Dietz C A Dunham E Dunn M E Ellerin T B Eron J J Fangman J J Farel C E Ferlazzo H Fidler S Fleenor-Ford A Frankel R Freedberg K A French N K Fuchs JD Fuller J D Gaberman J Gallant J E Gandhi R T Garcia E Garmon D Gathe J C Jr Gaultier C R Gebre W Gilman F D Gilson I Goepfert P A Gottlieb M S Goulston C Groger R K Gurley T D Haber S Hardwicke R Hardy W D Harrigan P R Hawkins T N Heath S Hecht F M Henry W K Hladek M Hoffman R P Horton J M Hsu R K Huhn G D Hunt P Hupert M J Illeman M L Jaeger H Jellinger R M John M Johnson J A Johnson K L Johnson H Johnson K Joly J Jordan W C Kauffman C A Khanlou H Killian R K Kim A Y Kim D D Kinder C A Kirchner J T Kogelman L Kojic E M Korthuis P T Kurisu W Kwon D S LaMar M Lampiris H Lanzafame M Lederman M M Lee D M Lee J M Lee M J Lee E T Lemoine J Levy J A Llibre J M Liguori M A Little S J Liu A Y Lopez A J Loutfy M R Loy D Mohammed D Y Man A Mansour M K Marconi V C Markowitz M Marques R Martin J N Martin H L Jr Mayer K H McElrath M J McGhee T A McGovern B H McGowan K McIntyre D Mcleod GX Menezes P Mesa G Metroka CE Meyer-Olson D Miller A O Montgomery K Mounzer K C Nagami E H Nagin I Nahass R G Nelson M O Nielsen C Norene D L O'Connor D H Ojikutu B O Okulicz J Oladehin O O Oldfield E C Olender S A Ostrowski M Owen WF Jr Pae E Parsonnet J Pavlatos A M Perlmutter A M Pierce M N Pincus J M Pisani L Price L J Proia L Prokesch R C Pujet H C Ramgopal M Rathod A Rausch M Ravishankar J Rhame F S Richards C S Richman D D Rodes B Rodriguez M Rose R C 3rd Rosenberg E S Rosenthal D Ross P E Rubin D S Rumbaugh E Saenz L Salvaggio M R Sanchez WC Sanjana V M Santiago S Schmidt W Schuitemaker H Sestak P M Shalit P Shay W Shirvani V N Silebi V I Sizemore J M Jr Skolnik P R Sokol-Anderson M Sosman J M Stabile P Stapleton J T Starrett S Stein F Stellbrink H J Sterman FL Stone V E Stone D R Tambussi G Taplitz R A Tedaldi E M Telenti A Theisen W Torres R Tosiello L Tremblay C Tribble M A Trinh P D Tsao A Ueda P Vaccaro A Valadas E Vanig T J Vecino I Vega V M Veikley W Wade B H Walworth C Wanidworanun C Ward D J Warner D A Weber R D Webster D Weis S Wheeler D A White D J Wilkins E Winston A Wlodaver C G van't Wout A Wright D P Yang O O Yurdin D L Zabukovic B W Zachary K C Zeeman B Zhao M | 2010 | Science2010，330，6010： | 1 |
| 11 | Influence of flour protein, extraction rate, particle size, and starch damage on the quality charaereristics of dry noodles 显示文摘 | Oh N H Seib P A Ward A B | 1985 | Cereal Chem1985，62，6： | 1 |
| 12 | Effect of Al and Organic Acids on the Surface Chemistry of Kaolinite显示文摘 | Ward D B Brady P V | 1998 | Clays and Clay Minerals1998，46，： | 1 |
| 13 | The internal phylogeny of ants (Hymenoptera :Formicidae)显示文摘 | Baroni Urbani C Bolton B Ward P S | 1992 | Syst Entomol1992，17，： | 1 |
| 14 | Modifiable Factors Associated With Improved Cardiac Arrest Survival in a Multicenter Basic Life Support/Defibrillation System: OPALS Study Phase I Results显示文摘 | Ian G Stiell George A Wells Valerie J DeMaio Daniel W Spaite Brian J Field Douglas P Munkley Marion B Lyver Lorraine G Luinstra Roxanne Ward | 1999 | Annals of Emergency Medicine1999，，： | 1 |
| 15 | Quantification and localization of FOXP3+ T lymphocytes and relation to hepatic inflammation during chronic HCV infection显示文摘 | Ward S M Fox B C Brown P J | 2007 | J Heptol2007，47，： | 1 |
| 16 | Genetic improvement of the Pacific oyster Crassostrea gigas(Thunberg)in Australia显示文摘 | Ward R D English L J McGoldrick D J Maguire G B Nell J A Thompson P A | | 0，，1： | 1 |
| 17 | Monitoring generators and large motors显示文摘 | Tamer P J Graydon B G Ward D M | 1986 | IEE Proceedings B1986，133，3： | 1 |
| 18 | Repair costs of 2 and 4 WD tractors显示文摘 | Ward S M McNulty P B Cunney M B | 1985 | Transactions of the ASAE1985，28，4： | 1 |
| 19 | Analysis of ammonia-oxidizing bacteria from hypersaline Mona Lake, California, on the basis of 16S rRNA sequences显示文摘 | WARD B B MARTINO D P DIAZ M C JOYE S B | 2000 | Applied and Environmental Microbiology2000，66，： | 1 |
| 20 | Influence of flour protein,extraction rate,particle size,and starch damage on the qualitycharacreristics of dry noodles显示文摘 | Oh N H Seib P A Ward A B | 1985 | Cereal Chem1985，62，6： | 1 |
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