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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 | Contrast-enhanced second-harmonic sonography in the detection of pseudocapsule in renal cell carcinoma显示文摘 | Ascenti G Gaeta M Magno C | 2004 | AJR Am J Roentgenol2004，182，6： | 1 |
| 3 | Glutathione S-transferases: an overview in cancer research显示文摘 | Di Pietro G Magno LA Rios-Santos F | 2010 | Expert Opin Drug Metah Toxicol2010，6，2： | 1 |
| 4 | Glutathione S-transferases:an overview in cancer research显示文摘 | Di Pietro G Magno LA Rios-Santos F | | 0，，： | 1 |
| 5 | Contrast-enhanced second-harmonic sonography in the edtection of pseudocapsule in renal cell carcinoma显示文摘 | Ascenti G Gaeta M Magno C | 2004 | AJRAm J Roentgenol2004，182，6： | 1 |
| 6 | Facile synthesis of meso-tetrakis(perfluoroalkyl)porphyrins:spectroscopic properties and X-ray crystal structure of highly electron-deficient 5,10,15,20-tetrakis(heptafluoropropyl)porphyrin显示文摘 | Di Magno S G Williams R A Therien M J | 1994 | J Org Chem1994，59，23： | 1 |
| 7 | Gas chromatography-mass spectrometry determination of 3-mercaptohexan-1-o1 and 3-mercaptohexyl acetate in wine A comparison ofheadspace solid phase microextraction and solid phase extraction methods显示文摘 | Fedrizzi B Versini G Lavagnini I Nicolini G Magno F | 2007 | Analytica Chimica Acta2007，596，： | 1 |
| 8 | Early onset lactating adenoma and the role of breast MRI: a case report显示文摘 | Magno S Terribile D Franeeschini G etal | 2009 | J Med Case Rep2009，3，： | 1 |
| 9 | Conservative and radical oneoplastic approches in the surgical treatment of breast cancer 显示文摘 | Franceschini G Magno S Fabbri C | 2008 | Eur Rev Med Pharmacol Sci2008，12，6： | 1 |
| 10 | Stereo-Based All-Terrain Obstacle Detection Using Visual Saliency显示文摘 | Pedro S Magno G Luis C el al | 2011 | Journal of Field Robotics2011，28，2： | 1 |
| 11 | Phase Ⅱ study of gemcitabine and cisplatin in patients with advanced or metastatic bladder cancer: long-term follow-up of a 3-week regimen 显示文摘 | Adamo V Magno C Spitaleri G | 2005 | Oncology2005，69，5： | 1 |
| 12 | Breast MRI in a case of 'early onset' lactating adenoma显示文摘 | Magno S Terribile D Franceschini G etal | 2009 | Breast J2009，15，1： | 1 |
| 13 | Contrast-enhanced second hamonic sonography in the detection of pscudocapsulc in renal cell carcinoma显示文摘 | Ascenti G Gacta M Magno C | 2004 | Am J Roentgenol2004，182，： | 1 |
| 14 | Contrast-enhanced second-hamonic sonography in the detection of pscudocapsulc in renal cell carcinoma显示文摘 | Ascenti G Gacta M Magno C | 2004 | Am J Roentgenol2004，182，6： | 1 |
| 15 | Early onset lactating adenoma and the role of breast MRI : a case report 显示文摘 | Magno S Terribile D Franceschini G | 2009 | J Med Case Reports2009，3，： | 1 |
| 16 | Hydroxychloroquine,in-decompensated,treatment refractory noninsnlin-dependent diabetes mellitus,a new job for an old drug显示文摘 | Quatraro A Consoli G Magno M | 1990 | Ann Intern Med1990，112，9： | 1 |
| 17 | Treatment of superficial bladder cancer with intravesical perfusion of rlL-2: A follow-up study 显示文摘 | Ferlazzo G Magno C Iemmo R | 1996 | Anticancer Res1996，16，2： | 1 |
| 18 | Glutathione S - trans- ferases:an overview in cancer research显示文摘 | Di Petro G Magno LA Rios - Santos F | 2010 | Expert Opin Drug Metab Toxieol2010，6，2： | 1 |
| 19 | Contrast-enhanced second- harmonic sonogmphy in the detection of pseudocapsule in renal cell carcinoma显示文摘 | Ascenti G Gaeta M Magno C | 2004 | Am J Roentgenol2004，182，： | 1 |
| 20 | Glow discharge electrolysis on methanol显示文摘 | Bontempelli G Magno F | 1973 | Electroanalytical Chemistry and Interfacial Electrochemistry1973，42，： | 1 |
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