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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 | Acute-on-chronic liver failure: Controversies and consensus显示文摘Acute-on-chronic liver failure(ACLF)is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease.Consequences include high short-term morbidity,mortality,and healthcare resource utilisation.ACLF encompasses a dysregulated,systemic inflammatory response,which can precipitate extra hepatic organ failures.Common precipitants include infection,alcoholic hepatitis,and reactivation of viral hepatitis although frequently no cause is identified.Heterogenous definitions,diagnostic criteria,and treatment guidelines,have been proposed by international hepatology societies.This can result in delayed or missed diagnoses of ACLF,significant variability in clinical management,and under-estimation of disease burden.Liver transplantation may be considered but the mainstay of treatment is organ support,often in the intensive care unit.This review will provide clarity around where are the controversies and consensus in ACLF including:Epidemiology and resource utilisation,key clinical and diagnostic features,strategies for management,and research gaps. | Natalie L Y Ngu Eliza Flanagan Sally Bell Suong T Le | 2023 | World Journal of Gastroenterology2023，29，2： | 2 |
| 3 | Isolation of Ty1-copia putative LTR sequences and their use as a tool to analyse genetic diversity in Olea europaea显示文摘 | NATALI L GIORDANI T BUTI M CAVALLINI A | 2007 | Mol Breeding2007，19，： | 1 |
| 4 | Microwave assisted Extraction as an alternative to soxhlet,sonieation, and supercriticalfluid extraction显示文摘 | VIORIA L A R/CHARD Y NATALY T | 1996 | Journal of Aoac International1996，79，1： | 1 |
| 5 | Nuclear DNA variability within Pisum sativum (Leguminosae) ; cytophotometrie analyses显示文摘 | CAVALLINI A NATALI L | 1990 | Plant Systematics and Evolution1990，173，34： | 1 |
| 6 | Nuclear DNA variability within Pisum sativum (Leguminosae) :nucleotypic effects on plant growth显示文摘 | CAVALLINI A NATALI L CIONINI G | 1993 | Heredity1993，70，： | 1 |
| 7 | Coronary athemsclerosis and alcohol consumption: angiographic and mortality data 显示文摘 | Femia R Natali A L' Abbate A et 81 | 2006 | Artetioacler Thromb Vase Biol2006，26，7： | 1 |
| 8 | β-Lactam antibiotic resistance:a current structural perspective显示文摘 | Mark S Wilke Andrew L Lovering Natalie CJ Strynadka | 2005 | Current Opinion in Microbiology2005，8，： | 1 |
| 9 | Experimental- numerical analysis of minipig's multi-rooted teeth 显示文摘 | Natali A N Camiel E L Pavan P G | 2007 | Journal of Biomechanies2007，40，8： | 1 |
| 10 | Metallothionein isoform expression by breast cancer cells显示文摘 | Natalie L Barnes M Leigh A | 2000 | Int J Biochem & Cell Biol2000，32，： | 1 |
| 11 | The development of a model of psychological first aid for non-mental health trained public health personnel: The Johns HopkinsRAPID-PFA 显示文摘 | George S E Lee M Natalie L S | 2014 | J Public Health Management Practice2014，20，5： | 1 |
| 12 | Long-term response to cal- cium-channel blockers in non-idiopathic pulmonary arterial hyper- tension 显示文摘 | Montani D Savale L Natali D | 2010 | Eur Heart J2010，31，15： | 1 |
| 13 | 显示文摘 | Natalie L | 2001 | Hear Res2001，162，： | 1 |
| 14 | Combined influences of mechanical properties and surface roughness on the tribologieal properties of amorphous carbon coatings显示文摘 | Naoki Fujisawa David R McKenzie Natalie L James | 2006 | Wear2006，260，12： | 1 |
| 15 | Coronary atherosclerosis and alcohol consumption: angiographic and mortality data 显示文摘 | Femia R Natali A L' Abbate A | 2006 | Arterioscler Thromb Vasc Bio12006，26，7： | 1 |
| 16 | Single-nucleotide polymorphisms in porcine mannan-binding lectin A显示文摘 | Brandon N L Natalie D K Squires E J | 2006 | Immunogenetics2006，58，12： | 1 |
| 17 | Use of fingerprinting and marker compounds for identification and standardization of botanical drugs: strategies for applying pharmaceutical HPLC analysis to herbal products 显示文摘 | Natalie L | 1998 | Drug InfJ1998，32，： | 1 |
| 18 | Retrotransposon-based molecu lar markers for grapevine species and cuhivars identification显示文摘 | D'ONOFRIO C LORENZIS G D GIORDANI T NATALI L CAVALHNI A SCALABRELIA G | 2010 | Tree Genetics Genomes2010，6，： | 1 |
| 19 | Character- ization and expression of DNA sequences encoding pu- tative type-II metallothioneins in the seagrass Posi- donia oceanica显示文摘 | Giordani T Natali L Maserti B E | 2000 | Plant Physiology2000，123，4： | 1 |
| 20 | Control of the critical dimension with a trilayer nanoimprint lithography procedure显示文摘 | Lebib A Natali M Li SP Cambril E Manin L Chen Y Janssen HM Sijbesma RP | 2001 | Micro-electron Engng2001，5758，： | 1 |
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