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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 | Micro-Spatial variability of soil nitrate following nitrogen fertilization and drip irrigation 显示文摘 | Zhang R D Vance G F Miller S D | 1999 | Water Air and Soil Pollution1999，116，： | 1 |
| 3 | Antithrombin efficiency is maintained in vitro in human plasma following dilution with hydroxyethyl starches显示文摘 | Vance G Nielsen | 2005 | Blood Coagulation & Fibrinolysis2005，，5： | 1 |
| 4 | Timber harvesting alters soil carbon mineralization and microbial community structure in coniferous forests显示文摘 | Chatterjee A Vance G F Pendall E | 2008 | Soil Biology & Biochemistry2008，40，： | 1 |
| 5 | Genetic heteroge- neity in HER-2 testing in breast cancer: panel summary and guidelines 显示文摘 | Vance G H Barry T S Bloom K J | 2009 | Arch Pathol Lab Med2009，13，4： | 1 |
| 6 | Fractional Partitioning for Assessing Sol-id-Phase Speciation and Geochemical Transformations of Soil Sele-nium显示文摘 | Sharmasarkar S Vance G F | 1995 | Soil Science1995，160，1： | 1 |
| 7 | Increasing rates of cardiac device infections among medicare beneficiaries: 1990–1999显示文摘 | Christopher H Cabell Paul A Heidenreich Vivian H Chu Christopher M Moore Martin E Stryjewski G.Ralph Corey Vance G Fowler | 2004 | American Heart Journal2004，，4： | 1 |
| 8 | The impact of speed of processing training on cognitive and everyday perform- ance 显示文摘 | Edwards J D Wadley V G Vance D E | 2005 | Azing Ment Health2005，9，3： | 1 |
| 9 | Incorporation ofuranium in zirconolite (CaZrTi2〇7)显示文摘 | VANCE E R LUMPKIN G R CARTER M L | 2002 | J Am Ceram Soc2002，85，7： | 1 |
| 10 | Plant viral suppressors of RNA silencing显示文摘 | Roth B M Pruss G J Vance V B | | 0，，1： | 1 |
| 11 | Secondary leukemias in refractory germ cell tumor patients undergoing autologous stem-cell transplantation using high-dose etoposide显示文摘 | Houck W Abonour R Vance G | | 0，，： | 1 |
| 12 | Pumping equipment for offshoredeep water & marginal oilfields显示文摘 | VANCE W KENT G | 2001 | World Pumps2001，419，： | 1 |
| 13 | Selenium adsorption on Mg-Al and Zn-Al layered double hydroxides显示文摘 | You Youwen Vance G F Zhao Hongting | 2001 | Applied Clay Science2001，20，12： | 1 |
| 14 | Fractional partitioning for assessing solid-phase speciation and geochemical transformations of soil selenium显示文摘 | Sharmasarkar S Vance G F | 1995 | Soli Sci1995，160，1： | 1 |
| 15 | Root carbon dioxide fixation by phosphorus-deficient Lupinus albus, Contribution to organic acid exudation by proteoid roots 显示文摘 | Johnson J F Allan D L Vance C P Weiblen G | 1996 | Plant Physiology1996，112，： | 1 |
| 16 | Selenium adsorption on Mg-Al and Zn-Al layered double hydroxides显示文摘 | You Y-W Vance G F Zhao H-T | 2001 | Applied Clay Science2001，20，12： | 1 |
| 17 | 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 |
| 18 | Taxol and cephalomannlne concentrations in the foliage and bark of shade grown and sun exposed Taxus brevifolia trees显示文摘 | Kelsey R G Vance N C | 1992 | J Nat Prod1992，55，7： | 1 |
| 19 | Taxol and cephalomannine concentrations in the foliage and bark of shade grown and sun exposed Taxus brevifolia trees显示文摘 | KELSEY R G VANCE N C | 1992 | Journal of Natural Products1992，55，7： | 1 |
| 20 | Acid phosphatase activity in phosphorus-deficient white lupin roots显示文摘 | Gilbert G A Knight J D Vance C P Allan D L | 1999 | Plant Cell and Environment1999，22，： | 1 |
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