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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 | How good is cap- sule endoscopy for detection of periampullary lesions? Results of a tertiary - referral center显示文摘 | CLARKE J O GIDAY S A MAGNO P | 2008 | Gastrointest Endosc2008，68，2： | 1 |
| 3 | Application of two- dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for proteomic analysis of the sexually ransmitted parasite Trichomonas vaginalis显示文摘 | Jose Batista De Jesus JB Patricia Cuervo P Magno Junqueira M | 2007 | J Mass Soectrom2007，42，11： | 1 |
| 4 | Is blood the i- deal submucosal cushioning agent A comparative study in a porcine model 显示文摘 | Giday SA Magno P Buscaglia JM | 2006 | Endoscopy2006，38，12： | 1 |
| 5 | The use of nitrite ion in the chromatographic determination of large amounts of hypochlorite ion and of traces of chlorite and chlorate ions显示文摘 | G-allina A Pastore P Magno F | 1999 | Analyst1999，124，10： | 1 |
| 6 | Association of hyper- tension, diabetes, dyslipidemia, and metabolic syndrome with obe- sity:finding from the National Health and Nutrition Examination Survey, 1990 to 2004显示文摘 | Nguyen N T Magno C P Lane K T | 2008 | J Am Coll Surg2008，207，6： | 1 |
| 7 | Stereo-based all-terrain obstacle detection using visual saliency显示文摘 | Santana P Magno Guedes Lufs Correia | | Field Robotics0，28，： | 1 |
| 8 | Natural orifice translumenal endoscopic surgery for anterior spinal procedures显示文摘 | Magno P Khashab MA Mas M | 2012 | Minim Invasive Surg2012，2012，36： | 1 |
| 9 | Complement protein Clq promotes macrophage anti-inflammatory M2-1ike po- larization during the clearance of atherogenic lipoproteins 显示文摘 | Spivia W Magno PS Le P | 2014 | Inflamm Res2014，63，10： | 1 |
| 10 | Is blood the ideal sub mucosal cushioning agent? A comparative study in a porcine model显示文摘 | Giday SA Magno P Buscaglia JM | 2006 | Endoscopy2006，1238，12： | 1 |
| 11 | Osteogenic differ- entiation ofpre-osteoblasts on biomimetic tyrosine-derived polycarbonate scaffolds 显示文摘 | Kim J Magno M H R Alvarez P | 2011 | Biomacromolecules2011，12，10： | 1 |
| 12 | Intraventricular thrombi with systemic embolization: two clinical cases显示文摘 | Magno P Freitas A Cunha P | 2006 | Rev Port Cardiol2006，25，2： | 1 |
| 13 | Infection during natural orifice transluminal endoscopic surgery : a randomized, controlled study in a live porcine model 显示文摘 | Giday SA Dray X Magno P | 2010 | Gastrointest Endosc2010，71，4： | 1 |
| 14 | Association of hypertension, diabetes, dyshpidemia, and metabolic syndrome with obesity: fmdings from the National Health and Nutrition Examination Survey, 1999 to 2004显示文摘 | NGUYEN N T MAGNO C P LANE K T | 2008 | J Am Coil Surg2008，207，6： | 1 |
| 15 | A new stapler-based full-thickness transgastric access closure: results from an animal pilot trial显示文摘 | MAGNO P GIDAY SA DRAY X | 2007 | Endoscopy2007，39，10： | 1 |
| 16 | Complement protein C1 q promotes macrophage anti-inflammatory M2-1ike polarization during the clear- ance of atherogenic lipoproteins 显示文摘 | Spivia W Magno PS Le P | 2014 | Inflamm Res2014，63，10： | 1 |
| 17 | Complement protein Clq promotes macrophage anti-inflammatory M2-1ike polarization during the clearance of atherogenic lipoproteins显示文摘 | Spivia W Magno PS Le P | 2014 | Inflamm Res2014，63，10： | 1 |
| 18 | Infection during natural orifice transluminal endoscopic surgery:a randomized,controlled study in a live porcine model显示文摘 | Giday SA Dray X Magno P | 2010 | Gastrointestinal endoscopy2010，71，4： | 1 |
| 19 | New nitroge- nous sesquiterpenes based on alloaromadendrane and epi- eudesmane skeletons from the marinesponge Axinella can- nabina显示文摘 | Ciminiello P Fattorusso E Magno S | 1987 | Can J Chem1987，65，3： | 1 |
| 20 | Sequestosome 1 mutations in Paget's disease of bone in Australia:prevalence,genotype/phenotype correlation,and a novel non-UBA domain mutation(P364S)associated with increased NF-kappaB signaling without loss of ubiquitin binding显示文摘 | Rea S L Walsh J P Ward L Magno A L Ward B K Shaw B Layfield R Kent G N Xu J | | 0，，07： | 1 |
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