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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 | Thermal maturity of the Barnett Shale determined from well-log analysis 显示文摘 | Hank Z Natalie B G Brad C | 2007 | AAPG Bulletin2007，91，4： | 1 |
| 3 | Prognostic factors in surgically resected N2 NSCLC : the importance of patterns of mediastinal lymph nodes metastases 显示文摘 | Casali C Stefani A Natali P | 2005 | Eur J Cardiothorac Surg2005，28，1： | 1 |
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| 5 | An IR image processing approach for characterizing combustion instability显示文摘 | CHIMENTI M NATALI DI C | 2004 | Infrared Physics & Technology2004，46，： | 1 |
| 6 | Water consumption of peach trees grafted on four different rootstocks 显示文摘 | NATALI S XILOYANNIS C BARBIERI A | 1985 | Aeta Hort1985，173，： | 1 |
| 7 | Arsenic fractionation in soils using an improved sequential extraction procedure显示文摘 | Walter W Wenzel Natalie Kirchbaumer Thomas Prohaska Gerhard Stingeder Enzo Lombi Domy C Adriano | 2001 | Analytica Chimica Acta2001，，2： | 1 |
| 8 | Motion analysis of Bryan cervical disc arthroplasty versus anterior diseeetomy and fusion:results from a prospective,randomized, multicenter, clinical trial显示文摘 | Rick C Natalie M Newton H | 2008 | J Spine Disord Tech2008，6，： | 1 |
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| 10 | Numerical analysis of tooth mobility: Formulation of a non-linear constitutive law for the periodontal ligament 显示文摘 | Natali A N Pavan P G Scarpa C | 2004 | Dental Materials2004，20，7： | 1 |
| 11 | Simultaneous Nitrification and Denitrification Using Stored Substrate (PHB) as the Electron Donor in an SBR显示文摘 | KATIE A T NATALIE B RALF C R | 2003 | Biotechnol Bioeng2003，83，： | 1 |
| 12 | Integrated analysis of metabolic phenotypes in Saccharomyces cerevisiae 显示文摘 | Natalie C Duarte | 2004 | BMC Genomics2004，5，： | 1 |
| 13 | Foot length in fetuses with abnormal growth显示文摘 | NATALIE B M CANDE V A JOHN C M | 2000 | J Ultrasound Med2000，19，： | 1 |
| 14 | Novel fiber-reinforced composite materials based on sustainable geopolymer matrix显示文摘 | NATALI A MANZI S BIGNOZZI M C | 2011 | Procedia Engineering2011，21，： | 1 |
| 15 | Anti - inflammatory and antioxidant properties of HDLs are impaired in type 2 diabetes 显示文摘 | Morgantini C Natali A Boldrini B | 2011 | Diabetes2011，60，10： | 1 |
| 16 | Changes in expression of alpha6/beta4 Integrin heterodimer in primary and metastatic breast cancer显示文摘 | Natali PG Nicotra MR Botti C | | 0，，2： | 1 |
| 17 | Heart rate monitoring in soccer:interest and limits during competitive match play and training, practical applica- tion显示文摘 | Alexandre D da Silva C D Hill-Haas S Wong del P Natali A J De Lima J R Bara Filho M G Matins J J Garcia E S Karim C | 2012 | J Strength Cond Res2012，26，10： | 1 |
| 18 | Development of a multiplex PCR assay for fine-scale population genetic analysis of the Komodo monitor Varanus komodoensis based on 18 polymorphic microsatellite loci 显示文摘 | Ciofi C Tzika A C Natali C | 2011 | Molecular Ecology Resources2011，511，3： | 1 |
| 19 | Heart rate monitoring in soccer: interest and limits during competitive match play and training, practical applica- tion显示文摘 | Alexandre D da Silva C D Hill-Haas S Wong del P Natali A J De Lima J R Bars Filho M G Matins J J Garcia E S Karim C | 2012 | J Strength C ond Res2012，26，10： | 1 |
| 20 | The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial显示文摘 | Natalie C Ward Jason HY Wu Michael W Clarke Ian B Puddey Valerie Burke Kevin D Croft Jonathan M Hodgson | 2007 | Journal of Hypertension2007，，1： | 1 |
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