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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 | 城市列车服役寿命评估显示文摘介绍了评估城市列车服役寿命和延长服役寿命的方法,以及风险评估的可靠性和随机方法。 | 阎锋(翻译) 赵云生(校) | 2020 | 国外铁道车辆2020，57，4： | 2 |
| 3 | Assessment of spatial memory in mice显示文摘 | Sharma S Rakoczy S Brown-Borg H | | 0，，17： | 1 |
| 4 | Long-living growth hormone receptor knockout mice:potential mechanisms of altered stress reaistance显示文摘 | Brown-Borg HM Rakoczy SG Sharma S | 2009 | Exp Gerontol2009，44，12： | 1 |
| 5 | Power consumption, mixing time, heat and mass transfer measurements for liquid vessels that are mixed using reciprocating multiplates agitators显示文摘 | Masiuk S Rakoczy R | 2007 | Chemical Engineering and Processing2007，46，： | 1 |
| 6 | Loss of the sulfate transporter Sic13a4 in placenta causes severe fetal abnormalities and death in mice显示文摘 | Joanna Rakoczy Zhe Zhang Francis Gerard Bowling Paul Anthony Dawson David Gordon Simmons | 2015 | Cell Research2015，25，11： | 1 |
| 7 | Testicular volume and semen parameters in patients aged 12 to 17 years with idiopathic varico- cele显示文摘 | Keene D J Sajad Y Rakoczy G | 2012 | J Pediatr Surg2012，47，2： | 1 |
| 8 | The potential ofmarrow stromal cells in tem cell therapy 显示文摘 | KICIC A SHEN W Y RAKOCZY P E | 2001 | Eye2001，15，6： | 1 |
| 9 | Matrix metalloproteinase (MMP) expression in experimental choroidal neovascularization 显示文摘 | Kvanta A Shen WY Sarman S Seregard S Steen B Rakoczy E | 2000 | Curr Eye Res2000，21，： | 1 |
| 10 | Pretence as Individual and Collective Intentionality显示文摘 | Hannes Rakoczy | 2008 | Mind & Language2008，23，5： | 1 |
| 11 | Inhibition of diclofenac formulated in hyaluronan on angiogenesis in vitro and its intraocular tolerance in the rabbit eye显示文摘 | Shen WY Constable IJ Chelva E Rakoczy PE | 2000 | Graefe Arch Clin Exp Ophthalmol2000，238，3： | 1 |
| 12 | Differentiation of marrow stromal cells into photoreceptors in the rat eye显示文摘 | Kicic A Shen WY Wilson AS Constable IJ Robertson T Rakoczy PE | 2003 | J Neurosci2003，23，21： | 1 |
| 13 | Inhibition of corneal neovascularization by recombinant adenovirus mediated antisense VEGF RNA显示文摘 | Lai CM Spilsbury K Brankov M Zaknich T Rakoczy PE | 2002 | Exp Eye Res2002，75，6： | 1 |
| 14 | Hyperbran - ched aliphatic polyethers obtained from environmentally benign monomer: Glycerols carbonate显示文摘 | G Rokicki P Rakoczy P Parzuchowski | 2005 | Green Chem2005，，7： | 1 |
| 15 | Differentiation of marrow stromal cells into photoreceptots in the rat eye 显示文摘 | Kicic A Shen WY Wilson AS Constable I J Robertson T Rakoczy PE | 2003 | J Neurosci2003，23，21： | 1 |
| 16 | Adenovirus and adeno- associated virus vectors 显示文摘 | Lai CM Lai YK Rakoczy PE | 2002 | DNA Cell Biol2002，21，12： | 1 |
| 17 | Progressive age-related changes similar to age-related macular degeneration in a transgenic mouse model显示文摘 | Rakoczy PE Zhang D Robertson T | 2002 | Am J Pathol2002，161，： | 1 |
| 18 | Nanoerystalline zeolite A:synthe- sis, ion exchange and dealumination 显示文摘 | Rakoczy R A Traa Y | 2003 | Mieroporous and Mesoporous Materials2003，60，： | 1 |
| 19 | Expression of cell adhesion molecules and vascular endothelial growth factor in experimental choroidal neovascularization in rat显示文摘 | Shen WY Yu MJ Barry CA Constable IJ Rakoczy PE | 1998 | Br J Ophthalmol1998，82，4： | 1 |
| 20 | Spatial memory is enhanced in long-living Ames dwarf mice and maintained following kainic acid induced neurodegeneration 显示文摘 | Sharma S Haselton J Rakoczy S | 2010 | Mech Ageing Dev2010，131，6： | 1 |
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