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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 | Transcranial doppler monitoring and clinical decision making after subarachnoid hemorrhage显示文摘 | Matthew J Robert P Larry B | 2003 | J Stroke Cerebrovascular Diseases2003，2，： | 1 |
| 5 | 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 |
| 6 | Marker gene elimination from transgenic barley,using co-transformation with adjacent' twin T-DNAs' on a standard Agrobacterium transformation vector显示文摘 | Matthews P R Wang B M | 2001 | Molecular Breeding2001，，7： | 1 |
| 7 | Laser capture microdissection (LCM) and comparative microarray expression analysis of syncytial cells isolated from incompatible and compatible soybean (Glycine max) roots infected by soybean cyst nematode (Heterodera glycines)显示文摘 | Klink V P Overall C C Alkharouf N MacDonald M H Matthews B F | | 0，，06： | 1 |
| 8 | 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 |
| 9 | The effect of graded concentrations of dietary DHA on growth, survival and tissue fatty acid profile of Senegal sole ( Solea senegalensis ) larvae during the Artemia feeding oeriod显示文摘 | Mireia V Alieia E Matthew P B | 2005 | Aquaculture2005，249，： | 1 |
| 10 | Marker gene elimination from transgenic barley,using cotransformation with adjacent 'twin T-DNAs' on a standard Agrobacterium transformation vector显示文摘 | Matthews P R Wang M B Waterhouse P M | 2001 | Molecular Breeding2001，7，： | 1 |
| 11 | Prediction of mammalian microRNA targets显示文摘 | Lewis B P Shih I H Matthew W J | 2003 | Cell2003，115，： | 1 |
| 12 | Laser capture microdissection (LCM) and expression analyses of Glycine max (soybean) syncytium containing root regions formed by the plant pathogen Heterodera glycines (soybean cyst nematode)显示文摘 | Klink V P Alkharout N MacDonald M Matthews B | | 0，，： | 1 |
| 13 | Marker gene elimination from transgenie barley, using eo- transformation with adjacent ' twin T-DNAs' on a standard Agrobacterium transformation vector 显示文摘 | MATTHEWS P R WANG M B WATERHOUSE P M | 2001 | Mol Breeding2001，7，： | 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 | Modification of Polyethylene Terephthalate (Dacron) Via Denier Reduction : Effects on Material Tensile Strength, Weight, and Protein Binding Capability显示文摘 | Matthew D P William C Q Martin J B | 1995 | Journal of Applied Biomaterials1995，，6： | 1 |
| 16 | Long-distance pollen flow assessment through evaluation of pollinator forag- ing range suggests transgene escape distances 显示文摘 | RE'MY S P Alexis P Matthew B H | 2008 | Proceedings of the National Academy of Sciences of the United States of America2008，105，13： | 1 |
| 17 | Characterization of human purified epithelial and stro- mal cells from endometrium and endometriosis in tissue culture显示文摘 | MATTHEWS C J REDFERM C P HIRST B H | 1992 | Fertil Steril1992，57，5： | 1 |
| 18 | Vortices in a Bose-Einstein condensate显示文摘 | MATTHEWS M R ANDERSON B P HALJAN P C | 1999 | Phys Rev Lett1999，83，13： | 1 |
| 19 | Development and testing of a model for predicting tillage effects on nitrate leaching from cracked clay soils显示文摘 | Matthews A M A C Armstrong P B Leeds-Harrison | 2000 | Soil and Tillage Research2000，53，： | 1 |
| 20 | 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 |
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