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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 | Endoscopic options for treatment of dysplasia in Barrett's esophagus显示文摘Recent advances in the endoscopic treatment of dysplasia in Barrett's esophagus(BE) have allowed endoscopists to provide effective and durable eradication therapies. This review summarizes the available endoscopic eradication techniques for dysplasia in patients with BE including endoscopic mucosal resection, endoscopic submucosal dissection, photodynamic therapy, argon plasma coagulation, radiofrequency ablation and cryotherapy. | R Brooks Vance Kerry B Dunbar | 2015 | World Journal of Gastrointestinal Endoscopy2015，7，19： | 3 |
| 3 | Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6显示文摘 | Vance C Rogelj B Hortobagyi T | 2009 | Science2009，323，： | 1 |
| 4 | Plant viral suppressors of RNA silencing显示文摘 | Roth B M Pruss G J Vance V B | | 0，，1： | 1 |
| 5 | RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets:implications for pediatric immunotherapy显示文摘 | Coughlin C M Vance B A Grupp S A | 2004 | Blood2004，103，6： | 1 |
| 6 | Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6 显示文摘 | Vance C Rogelj B HortobOgyi T | 2009 | Science2009，323，5918： | 1 |
| 7 | Topsoil depth effects on reclaimed coal mine and native area vegetation in northeastern Wyoming显示文摘 | Schladweiler B K Vance G F Legg D E | 2005 | Rangeland Ecology and Management2005，58，2： | 1 |
| 8 | 显示文摘 | Vance E R Nowotny J E | 1994 | J Am Ceram Soc1994，77，： | 1 |
| 9 | Characterization of solid and dissolved carbon in a spruce-fir Spodosol显示文摘 | Dai K H David M B Vance G F | 1996 | Biogeo- chemistry1996，35，2： | 1 |
| 10 | Plant viral suppressors of RNA silencing显示文摘 | ROTH M PRUSS J VANCE B | 2004 | Virus Research2004，102，： | 1 |
| 11 | An improved method for calculating gritical speeds and rotor-dynamic stability of turbomachinery显示文摘 | Murphy B T Vance J M | 1983 | Trans of ASME for Power1983，1983，： | 1 |
| 12 | Explaining and predicting the impact of branding alliances and web site quality on initial consumer trust of e-commerce web sites显示文摘 | Lowry P B Vance A Moody G Beckman B Read A | | 0，，04： | 1 |
| 13 | 5'Proximal potyviral sequence mediate potato viruis X potyviral synergistic diseases in transgenic tobacco显示文摘 | VANCE V B BERGER P H CARRINGTON J C | 1995 | Virology1995，206，1： | 1 |
| 14 | Lo-calization of superoxide dismutases and hydrogen peroxide in legume root nodules 显示文摘 | Rubio M C James E K Clemente M R Bucciarelli B Fedorova M Vance C P Becana M | 2004 | Molecular Plant-Microbe Interactions2004，17，12： | 1 |
| 15 | Effect of Particle Size on the Roem-Tempereture Crystal Structure of Barium Titanate 显示文摘 | Begg B D Vance E R Nowotny J | 1994 | Journal of the American Ceramic Society1994，77，12： | 1 |
| 16 | RNA silencing in plants - defense and counterdefense显示文摘 | Vance V B Vaucheret H | 2001 | Science2001，292，5525： | 1 |
| 17 | Size Driven Phase Transition of Barium Titanate Nanoparticles Prepared by Plasma Chemical Vapor Deposition 显示文摘 | Begg B D Vance E R Nowotny J | 1994 | Journal of theAmerican Ceramic Society1994，77，12： | 1 |
| 18 | Birdsfoot trefoil (Lotus corniculatus) root nodules:morphogenesis and the effect of forage harvest on structure and function显示文摘 | Vance C P Johnson L E B Stade S | | 0，，04： | 1 |
| 19 | Human CD69 associates with an N-termianalfragment of calreticulin at the cell surface 显示文摘 | VANCE B A HARLEY P H BACKLUND P S etal | 2005 | ArchBiochem Biophys2005，438，1： | 1 |
| 20 | Chemistry of dissolved organic carbon at Bear Brook Watershed, Maine: stream water response to ( NH4 )2 SO4 additions显示文摘 | David M B Vance G Kahl J | 1999 | Environmental Monitoring and Assessment1999，55，： | 1 |
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