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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 | Negative and positive effects of topsoil biological crusts on water availability along a rainfall gradient in a sandy arid area 显示文摘 | Ram A Aaron Y | 2007 | Catena2007，70，： | 1 |
| 3 | Estimating the lesbian population : a capture - recapture approach 显示文摘 | AARON D J CHANG Y F MARKOVIC N | 2003 | J Epidemiol Community Heahh2003，57，： | 1 |
| 4 | Creation and preliminary characterization of a leptin knockout rat显示文摘 | Serglo V Chang Y Aaron M | 2012 | Endocrinology2012，153，11： | 1 |
| 5 | Sequential Exposure to Carbon Nanotubes and Bacteria Enhances Pulmonary Inflammation and Infectivity显示文摘 | Shvedova Anna A Fabisiak James P Kisin Elena R Murray Ashley R Roberts Jenny R Tyurina Yulia Y Antonini James M Feng Wei Hong Kommineni Choudari Reynolds Jeffrey Barchowsky Aaron Castranova Vince Kagan Valerian E | 2008 | American Journal of Respiratory Cell and Molecular Biology2008，，5： | 1 |
| 6 | Genotype-phenotype correlation between the polymorphic UGT2B17 gene deletion and NNAL glucuronidation activities in human liver microsomes 显示文摘 | Lazarus P Zheng Y Aaron Runkle E | 2005 | Pharmacogenet Genomics2005，15，11： | 1 |
| 7 | International waters: identifying basins at risk 显示文摘 | AARON T W SHIRA B Y MARK G | 2003 | Water Policy2003，，5： | 1 |
| 8 | Experimental investigation of a bridge girder made of steel tube filled with concrete 显示文摘 | Nazanin M Aaron Y Atorod A | 2005 | Journal of Constructional Steel Research2005，，61： | 1 |
| 9 | Synthesis and Structure of (Triphenylsilyl)imido Complexes of Titanium and Zirconium显示文摘 | LI Y H SANJUKTA B J AARON L O | 2005 | Organometallics2005，24，： | 1 |
| 10 | Understanding long-term changes in microbial fuel cell performance using electrochemical impedance spectroscopy 显示文摘 | Borole A P Aaron D Hamilton C Y | 2010 | Environmental Science and Technology2010，44，7： | 1 |
| 11 | Bone versus immune system显示文摘 | Aaron J Choi Y | 2000 | Nature2000，408，6812： | 1 |
| 12 | Negative and positive effects of topsoil biological crusts on water availability along a rainfall gradient in a sandy arid area显示文摘 | RAM A AARON Y | 2007 | Catena2007，70，： | 1 |
| 13 | Understand- ing long-term changes in microbial fuel cell performance using electrochemical impedance spectroscopy显示文摘 | BOROLE A P AARON D HAMILTON C Y | 2010 | Environmental Sci- ence and Technology2010，44，7： | 1 |
| 14 | Representation learning: a review and new perspectives 显示文摘 | BENGIO Y Aaron courville and Pascal Vincent | 2013 | IEEE Transaction on pattern analysis and machine intelligence2013，38，8： | 1 |
| 15 | Creation and preliminary character- ization of a leptin knockout Rat 显示文摘 | Serglo V Chang Y Aaron M | 2012 | Endocrinology2012，153，11： | 1 |
| 16 | Creation and preliminary characterization of a leptin knockout Rat 显示文摘 | Serglo V Chang Y Aaron M | 2012 | Endocrinology2012，153，11： | 1 |
| 17 | Understanding long-termchanges in microbial fuel cell performance using electrochemicalimpedance spectroscopy 显示文摘 | Borole A P Aaron D Hamilton C Y | 2010 | Environmental Science & Technology2010，44，7： | 1 |
| 18 | Controversial role of arthroscopic meniscectomy of the knee: A review显示文摘The role of arthroscopic partial meniscectomy(APM) in reducing pain and improving function in patients with meniscal tears remains controversial. Five recent highquality randomized controlled trials(RCTs) compared non-operative management of meniscal tears to APM, with four showing no difference and one demonstrating superiority of APM. In this review, we examined the strengths and weaknesses of each of these RCTs, with particular attention to the occurrence of inadvertent biases. We also completed a quantitative analysis that compares treatment successes in each treatment arm, considering crossovers as treatment failures. Our analysis revealed that each study was an excellent attempt to compare APM with non-surgical treatment but suffered from selection, performance, detection, and/or transfer biases that reduce confidence in its conclusions. While the RCT remains the methodological gold standard for establishing treatment efficacy, the use of an RCT design does not in itself ensure internal or external validity. Furthermore, under our alternative analysis of treatment successes, two studies had significantly more treatment successes in the APM arm than the non-operative arm although original intention-totreat analyses showed no difference between these two groups. Crossovers remain an important problem in surgical trials with no perfect analytical solution. With the studies available at present, no conclusion can be drawn concerning the optimal treatment modality for meniscal tears. Further work that minimizes significant biases and crossovers and incorporates sub-group and cost-benefit analyses may clarify therapeutic indications. | Austin Y Ha Robert M Shalvoy Anne Voisinet Jennifer Racine Roy K Aaron | 2016 | World Journal of Orthopedics2016，7，5： | 1 |
| 19 | Hydrological processes in a small arid catchment: Scale effects of rainfall and slope length 显示文摘 | Aaron Y Naama R Y | 2004 | Geomorphology2004，61，12： | 1 |
| 20 | A histochemical method for the demonstration of calcifying cartilage显示文摘 | Aaron RK Jol y G Ciombor DM | | 0，，04： | 1 |
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