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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 | An extraction method for measuring soil microbial biomass C显示文摘 | Vance E D Brooks P C Jenkinson D S | 1987 | Soil Biology and Biochemistry1987，19，6： | 1 |
| 3 | Phytoremediation of soil contaminated with low concentrations of radionuclides显示文摘 | Entry J A Vance N C Hamilton M A | 1996 | Water Air Soil Pollution1996，88，： | 1 |
| 4 | An extraction method for measuring soil microbial biomass显示文摘 | Vance E D Brookes P C Jenkinson D S | 1987 | Soil Biology & Biochemistry1987，19，： | 1 |
| 5 | An extraction meth-od for measuring soil microbial biomass C显示文摘 | Vance E D Brookes P C jenkinson D S | 1987 | Soil Biology^Biochemistry1987，19，6： | 1 |
| 6 | An Extraction Method for Measuring Soil Microbial Biomass C 显示文摘 | Vance E D Brookes P C Jenkinson D S | 1987 | Soil Biol- ogy and Biochemistry1987，19，6： | 1 |
| 7 | The impact of urban form on automobile travel : Disentangling causation from correlation 显示文摘 | Vance C Hedel R | 2007 | Transporta- tion2007，34，5： | 1 |
| 8 | Are Society Responsible Corporations Good Investment Risks? 显示文摘 | Vance S C | 1975 | Management Review1975，，8： | 1 |
| 9 | An extraction method for measuring soil microbial biomass C显示文摘 | VANCE E D BROOKES P C JENKISON D C | 1987 | Soil Biol Biochern1987，19，： | 1 |
| 10 | The determination of the isotopic composition of Cu and Zn in seawater显示文摘 | BERMIN J VANCE D ARCHER C | 2006 | Chemical Geology2006，226，34： | 1 |
| 11 | An extraction method for measuring soil microbial biomass C 显示文摘 | VANCE E D BROOKES P C JENKINSON D S | 1987 | Soil Biology and Biochemistry1987，19，6： | 1 |
| 12 | The Economic: Design of Control Charts:A Unified Approach显示文摘 | Lorenzen T J Vance L C | 1986 | Technometrics1986，，28： | 1 |
| 13 | An extraction method for measuring microbial biomass C 显示文摘 | Vance D Brookes P C Jenkinson D S | 1987 | Soil Biology and Biochemistry1987，19，： | 1 |
| 14 | An extraction method for measuring microbial biomass C显示文摘 | Vance E D Brookes P C Jekinson D S | 1987 | Soil Biology and Biochemistry1987，19，6： | 1 |
| 15 | Phytoremediation of soil contaminated with low concentrations of radionuclides显示文摘 | Entry J A Vance N C Hamilton | 1996 | Water Air and Soil Pollut1996，88，12： | 1 |
| 16 | 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 |
| 17 | Transgenic alfalfa secretes a fungal endochitinase pro- tein to the rhizospere 显示文摘 | TESFAYE M DENTON M D VANCE C P | 2005 | Plant and Soil2005，269，12： | 1 |
| 18 | Phosphorus acquisition and use: critical adaptations by plants for securing a nonrenewable resource显示文摘 | VANCE C P UHDE-STONE C ALLAN D L | 2003 | New Phytologist2003，157，3： | 1 |
| 19 | Impacts of elevated N inputs on north temperate forest soil C storage,C/N,and net N- mineralization显示文摘 | Nave L Vance EED Swanston C W | 2009 | Geoderma2009，153，12： | 1 |
| 20 | An extrac- tion method for measuring soil microbial biomoss C显示文摘 | Vance E D Brookes P C ]enkinsmx D S | 1987 | Soil Biology and Biochemistry1987，19，6： | 1 |
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