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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 | Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study显示文摘 | Julia Granerod Helen E Ambrose Nicholas WS Davies Jonathan P Clewley Amanda L Walsh Dilys Morgan Richard Cunningham Mark Zuckerman Ken J Mutton Tom Solomon Katherine N Ward Michael PT Lunn Sarosh R Irani Angela Vincent David WG Brown Natasha S Crowcroft | 2010 | The Lancet Infectious Diseases2010，，12： | 2 |
| 3 | A novel plasminogen activator from Streptococcus uberis显示文摘 | Rosey E L Lincoln R A Ward P N | 1999 | FEMS Microbiol Lett1999，178，： | 1 |
| 4 | Pneumonia: high-resolu tion CT findings in 114 patients显示文摘 | Reittner P Ward S Heyneman L | 2003 | Eur Radiol2003，13，3： | 1 |
| 5 | Exploratory spatial data analysis of regional seroprevalence of antibodies against epizootic hemorrhagic disease virus in cattle from Illinois and Indiana 显示文摘 | BOYER T C WARD M P WALLACE R L | 2008 | American Journal of Veterinary Research2008，69，： | 1 |
| 6 | Rapid Radiation Events in the Family Ursidae Indicated by Likihood Phylogenetic Estimationfrom Multiple Fragments of mtDNA 显示文摘 | Waits L P O'Brien S J Ward R H | 1999 | Mol Phylogenet Evol1999，13，1： | 1 |
| 7 | 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 |
| 8 | Coordinate gene activity in response to agents that in- duce systemic acquired resistance显示文摘 | WARD E R UKNESS S J WILLIAMS S C DINCHER S S WIEDER- HOLD D L ALEXANDER D C AHL-GOY P METRAUX J P RYALS J A | 1991 | Plant Cell1991，3，10： | 1 |
| 9 | Spacecraft Attitude Estima- tion Using the Global Positioning System: Method- ology and Results for RADCAL显示文摘 | Axelrad P Ward L M | 1996 | Journal of Guidance Control and Dynamics1996，19，： | 1 |
| 10 | MIC- 1 se- rum level and genotype : associations with progress and prognosis of colorectal carcinoma显示文摘 | BROWN D A WARD R L BUCKHAULTS P | 2003 | Clin Cancer Res2003，9，7： | 1 |
| 11 | Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation显示文摘 | Jaime L Tartar Christopher P Ward James T McKenna | | 0，，10： | 1 |
| 12 | A scientific note on the detection of honeybee viruses using real-time PCR(TaqMan)in Varroamites collected from a Thai honeybee(Apis mellifera)apiary显示文摘 | Chantawannakul P Ward L Boonham N Brown M | 2006 | J Invertebr Pathol2006，91，1： | 1 |
| 13 | Production and Characterization of a Biosurfactant Isolated from Pseudomonas aeruginosa UW-1 显示文摘 | SIM L WARD O P LI Zy | 1997 | Ind Microbiol Biotechnol1997，19，4： | 1 |
| 14 | Global catastrophes in earth his- tory: An interdisciplinary conference on impacts, volcan- ism, and mass mortality显示文摘 | Sharpton V L Ward P D | 1990 | Geological Society of America Special Paper1990，，247： | 1 |
| 15 | 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 |
| 16 | Hyaluronic acid: its role in voice显示文摘 | WARD P D THIBEAULT S L GRAY S D | 2002 | J Voice2002，16，3： | 1 |
| 17 | Production and characterisation of a biosurfactant isolated from Pseudomonas aeruginosa UW-1显示文摘 | L Sim O P Ward Z-Y Li | 1997 | Journal of Industrial Microbiology & Biotechnology1997，，4： | 1 |
| 18 | MIC-1 ser-um level and genotype:associations with progress and prognosis ofcolorectal carcinoma显示文摘 | BROWN D A WARD R L BUCKHAULTS P | 2003 | Clin Cancer Res2003，9，7： | 1 |
| 19 | 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 |
| 20 | Production and characterization of a biosurfactant isolated form Pseudomonas aeruginosa UW-1显示文摘 | Sim L Ward O P Li Z Y | 1997 | Journal of Industrial Microbiology and Biotechnology1997，19，4： | 1 |
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