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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 | Cloning and mapping of variety-speeific rice genomic DNA sequences:amplifled fragment length polymorphisms(AFLP)from silver-stained Polyaerylamide gels显示文摘 | Yong G C MattheW w B OliVier P et a1 | 1996 | Genome1996，39，： | 1 |
| 3 | Adaptation of HIV-1to human leukocyte antigen class I显示文摘 | Kawashima Y Pfafferott K Frater J Matthews P Payne R Addo M Gatanaga H Fujiwara M Hachiya A Koizumi H Kuse N Oka S Duda A Prendergast A Crawford H Leslie A Brumme Z Brumme C Allen T Brander C Kaslow R Tang J Hunter E Allen S Mulenga J Branch S Roach T John M Mallal S Ogwu A Shapiro R Prado J G Fidler S Weber J Pybus O G Klenerman P Ndung'u T Phillips R Heckerman D Harrigan P R Walker B D Takiguchi M Goulder P | 2009 | Nature2009，458，7238： | 1 |
| 4 | Variable structure control of nonlinear multivariable systems: a tutorial 显示文摘 | de Carlo R A Zak S H Matthews G P | 1988 | Proceedings of the IEEE1988，76，3： | 1 |
| 5 | A randomized trial of tigecycline versus ampicillin-sulbactam or amoxicillin-cla-vulanate for the treatment of complicated skin and skin struc- ture infections显示文摘 | Matthews P Alpert M Rahav G | 2012 | BMC Infect Dis2012，12，： | 1 |
| 6 | A randomized trial of tigecycline versus ampicillin-sulbactam or amoxicillin- clavulanate for the treatment of complicated skin and skin structure infe,ctions显示文摘 | Matthews P Alpert M Rahav G | 2012 | BMC Infect Dis2012，12，： | 1 |
| 7 | Extraction and characterisation of lipids from Antarctic krill (Euphausia superba)显示文摘 | JOSEPH C G MATTHEW P D SARAH K B | 2010 | Food Chemistry2010，125，3： | 1 |
| 8 | Variable structure control of nonlinear multivariable systems: A tutorial 显示文摘 | DeCarlo R A Zak S H Matthews G P | 1988 | IEEE Proceeding1988，76，： | 1 |
| 9 | Acute endophthalmitis following intravitreal triamcinolone acetonide injection显示文摘 | Darius M Moshfeghi Peter K Kaiser Ingrid U Scott Jonathan E Sears Matthew Benz Juan P Sinesterra Richard S Kaiser Sophie J Bakri Raj K Maturi Jonathan Belmont Paul M Beer Timothy G Murray Hugo Quiroz-Mercado William F Mieler | 2003 | American Journal of Ophthalmology2003，，5： | 1 |
| 10 | Extraction and characterization of lipids from Antarctic krill(Euphausia superba)显示文摘 | Joseph C G Matthew P D Sarah K B | 2011 | Food Chemistry2011，，125： | 1 |
| 11 | Changes in IGFs in cardiac tissue following myocardial infarction显示文摘 | Matthews K G Devlin G P Conaglen J V | 1999 | J Endocrinol1999，163，3： | 1 |
| 12 | A sensor for in situ indicator-based measurements of seawater pH显示文摘 | MATTHEW P SEIDEL M D DEGRANDPRE A G | 2008 | Marine Che- mistry2008，109，： | 1 |
| 13 | Morphological and physiological effects of water deficit and endophyte infection on contrasting tall rescue cultivars 显示文摘 | Assuero S G Matthew C Kemp P D | 2000 | New Zealand Journal of Agricultural Research2000，43，： | 1 |
| 14 | Characterization of polyploid wheat genomic diversity using a high-density 90 000 single nucleotide polymorphism array 显示文摘 | Wang SC Debbie W Kerrie F Alexandra A Shiaoman C Bevan EH Marco M Silvio S Sara GM Luigi C Anna MM Alex W Stuart S Gary B Ralf W Joerg P International Wheat Genome Sequencing Consortium Morten L Diane M Rudi A Rudy D Gina BG Abraham K Alina RA Catherine F Jerome S Michele M Curtis P Luo MC Jan DMM Jorge D Martin G Roberto T Cindy L Ivan M Colin C Keith JE Matthew H Eduard A | 2014 | Plant Biotechnol J2014，12，： | 1 |
| 15 | Use of Waste Tire Steel Beads in Portland Cement Concrete显示文摘 | Christos G P Matthew J T | 2006 | Cement of Concrete Research2006，36，9： | 1 |
| 16 | Variable structurecontrol of nonlinear multivariable systems:a tutorial显示文摘 | DECARLO R A ZAK S H MATTHEWS G P | 1988 | Proceed-ings of the IEEE1988，76，3： | 1 |
| 17 | Mass fractionation processes of transition metal isotopes显示文摘 | Zhu X K Guo Y Williams R J P O'Nions R K Matthews A Belshaw N S Canters G W de Waal E C Weser U Burgess B K Salvato B | 2002 | Earth Planet Sci Lett2002，200，12： | 1 |
| 18 | Implications of task-induced fatigue effects for in-vehicle countermeasures to driverfatigue显示文摘 | Desmond P A Matthews G | 1997 | Accident Analysis and Prevention1997，29，4： | 1 |
| 19 | SCN5A mutations associate with arrhythmic dilated cardiomy- opathy and commonly localize to the voltage-sensing mecha- nism 显示文摘 | WILLIAM P M GIANFRANCO S MATTHEW R G T | 2011 | Journal of the American College of Cardiology2011，57，21： | 1 |
| 20 | Stabilization mechanisms of hindered amines 显示文摘 | PETER P KLEMCHUK G MATTHEW E | 1988 | Polymer Degradation and Stability1988，22，3： | 1 |
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