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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 | Comparison of six RNA extraction methods for the detection of classical swine fever virus by real-time and conventional reverse transcription-PCR 显示文摘 | DENG M Y WANG H WARD GB | 2005 | J Vet Diagn Invest2005，17，6： | 1 |
| 3 | Oxide formation of K38G superalloy and its sputtered micrograined coating显示文摘 | Ward F H | 1994 | Surf Coat Technol1994，63，： | 1 |
| 4 | Topoisomerase II- mediated breaks in spermatozoa cause the specific degradation of paternal DNA in fertilized oocytes显示文摘 | Yamauchi Y Shaman JA Ward WS | 2007 | Biol Reprod2007，76，4： | 1 |
| 5 | Trends in the leading causes of death in the United States,1970-2002显示文摘 | JEMAL A WARD E HAO Y | 2005 | Jama2005，294，10： | 1 |
| 6 | Changes in the sertun proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis显示文摘 | Ward D G Cheng Y N'Kontehou G | 2006 | Br J Cancer2006，94，2： | 1 |
| 7 | Cellular and subcellular calcium accumulation during glutamateinduced injury in cerebellar granule neurons显示文摘 | Ward MW Kushnareva Y Greenwood S | 2005 | J Neurochem2005，92，5： | 1 |
| 8 | The CXC chemokine stromal cell-derived factor activates a Gi-coupled phosphoinositide 3-kinase in T lymphocytes 显示文摘 | Sotsios Y Whittaker G C Westwick J Ward S G | 1999 | J Immunol1999，163，： | 1 |
| 9 | Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus: population based study of coronary heart disease显示文摘 | Danesh J Wong Y Ward M | 1999 | Heart1999，81，3： | 1 |
| 10 | Evapotranspiration components determined by sap flow and microlysimetry techniques of a vineyard in northwest China: Dynamics and influential factors显示文摘 | Zhang Y Kang S Ward E J | 2011 | Agricultural Water Management2011，98，8： | 1 |
| 11 | Oxidation of 4-bromophenol by recombinant cellulose binding domain horseradish peroxidase fused protein immobilized to cellulose显示文摘 | Ward G Hadar Y | 2003 | Biotechnol Bioeng2003，82，： | 1 |
| 12 | Phosphoinositide 3-kinase:a key biochemical signal for cell migration in response to chemokines显示文摘 | Sotsios Y Ward SG | 2000 | Immunol Rev2000，177，10： | 1 |
| 13 | Genetic scheduling for parallel processor systems:Comparative studies and performance issues显示文摘 | Zomaya A Y Ward C and Macey B | 1999 | IEEE Trans Parallel and Distributed Systems (S1045-9219)1999，10，8： | 1 |
| 14 | Effect of heat-moisture treatment on the formation and physicochemical properties of resistant starch from mung bean (Phaseolus radiatus) starch显示文摘 | Li S L Ward R Gao Q Y | 2011 | Food Hydrocolloids2011，25，7： | 1 |
| 15 | High pressure combustion and flames in supercritical fluid显示文摘 | ARMSTRONG D W TANG Y WARD T | 1993 | Anal Chem1993，65，： | 1 |
| 16 | Effect of cancer pain on performance status, mood states, and level of hope among Taiwanese cancer patients显示文摘 | Lin C C Lai Y L Ward S E | 2003 | Journal of Pain and Symptom Management2003，25，1： | 1 |
| 17 | Hepatic artery dexamethasone infusion inhibits colorectal hepatic metastases: a regional antiangiogenic therapy显示文摘 | Arisawa Y Sutanto -Ward E Fortunato L | 1995 | Ann Surg Oncol1995，2，2： | 1 |
| 18 | Signal pathways which promote invasion and metastasis: critical and distinct contributions of extracellular signal-regulated kinase and Ral-specific guanine exchange factor pathways显示文摘 | Ward Y Wang W Woodhouse E | 2001 | Mol Cell Biol2001，21，： | 1 |
| 19 | Biomass production from selected herbaceous species in the Southeastern USA显示文摘 | Bransby D I Ward C Y Rose P A etal | 1989 | Biomass1989，20，12： | 1 |
| 20 | Placental inflammation and oxidative stress in the mouse model of assisted reproduction显示文摘 | Raunig J M Yamauchi Y Ward M A | 2011 | Placenta2011，32，11： | 1 |
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