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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 | Analysis of prognostic factors in patients with isolated chest wall recurrence of breast cancer 显示文摘 | MAGNO L BIGNARDI M MICHELETTI E | 1987 | Cancer1987，60，： | 1 |
| 3 | Jiggling the tropical thermostat in the Cretaceous hothouse显示文摘 | Bice K L Magno E A | 2002 | Geology2002，30，： | 1 |
| 4 | A low power wireless node for contact and contactless heart monitoring显示文摘 | Magno M Spagnol C Benini L | 2014 | Microelectronics Journal2014，45，12： | 1 |
| 5 | The calciurn-scnsing receptor: a molecular perspective显示文摘 | Magno A L Ward B K Ratajczak T | 2011 | Endocr Rcv2011，32，1： | 1 |
| 6 | Induction of chemokines and chemokine receptors CCR2b and CCR4 in authentic human osteoclasts differentiated with RANKL and osteoclast like cells differentiated by MCP-1 and RANTES显示文摘 | Kim M S Magno C L Day C J | 2006 | J Cell Biochem2006，97，3： | 1 |
| 7 | Jiggling the tropical thermostat in the Cretaceous hothouse显示文摘 | Norris R D Bice K L Magno E A | 2002 | Geology2002，30，4： | 1 |
| 8 | Monte Carlo simulation of the size and composition of bimetallic nanoparti cles synthesized in water in oil microemulsions显示文摘 | Angelescu D G Magno L M Stuhenrauch C | 2010 | Journal of Physical Chemistry C2010，114，22： | 1 |
| 9 | Cat scratch disease in primary care显示文摘 | Magno S L Spatar L | 2009 | J Nurse Practitioners2009，5，5： | 1 |
| 10 | Sterols of mediterranean cholrophyceae显示文摘 | Fattorusso E Magno S Mayol L | 1980 | Experientia1980，36，10： | 1 |
| 11 | New tetracyclic analogues of photochemotherapeutic drugs 5-MOP and 8-MOP: synthesis, DNA interaction, and antiproliferative activity 显示文摘 | Dalla Via L Gia O Marciani Magno S | 1999 | J Med Chem1999，42，： | 1 |
| 12 | Combined surgical and endoscopic approachfor the reduction of a congenital hiatal hernia in a cat: a case report显示文摘 | Pisoni L Del Magno S Cinti F | 2014 | Vet Med (Praha)2014，59，3： | 1 |
| 13 | New tetracyclic analogues of photochemotherapeutic drugs 5-MOP and 8-MOP: synthesis, DNA interac- tion, and antiproliferative activity显示文摘 | Dalla Via L Gia O Marciani Magno S | 1999 | J Med Chem1999，42，21： | 1 |
| 14 | Influence of Thermomechanical Parameters on the Competi- tion Between Dynamic Reerystallization and Dynamic Strain In duced Transformation in C-Mn and C Mn-Nb Steels Deformed by Hot Torsion 显示文摘 | Ferreira J L Tulio Magno F de Melo Iavni de Souza Bott | 2007 | ISIJ International2007，47，11： | 1 |
| 15 | Unusual case of calcified renal fibroma显示文摘 | Inferrera A D' Arrigo L Magno C | 2000 | Arch Ital Urol Androl2000，72，2： | 1 |
| 16 | Benzothiopyranoin- dole-based antiproliferative agents: synthesis, cytotoxicity, nucleic acids interaction, and topoisomerases inhibition prop- erties显示文摘 | Dalla Via L Magno SM Gia O | 2009 | J MedChem2009，52，17： | 1 |
| 17 | Correlation of proliferative index (PCNA reactivity and Ki- 67 reactivity) in primary breast carcinoma with hormore status,lymph node status and disease- free survival 显示文摘 | Hirschfield L Bhuiya T | 1992 | Conn Med1992，56，12： | 1 |
| 18 | Sequestosome 1 mutations in Paget's disease of bone in Australia:prevalence,genotype/phenotype correlation,and a novel non-UBA domain mutation(P364S)associated with increased NF-kappaB signaling without loss of ubiquitin binding显示文摘 | Rea S L Walsh J P Ward L Magno A L Ward B K Shaw B Layfield R Kent G N Xu J | | 0，，07： | 1 |
| 19 | 肝切除治疗八个或更多结肠癌肝脏转移灶显示文摘背景:对于具有大量肝转移灶的结肠癌病人,手术切除可能是有效的治疗方法,但其确切的益处尚不清楚。方法从两个具有大样本容量的肝脏外科中心收集1998至2012年间施行手术切除的结肠癌肝转移的病人数据,并根据其转移灶的数量进行分组:组1(转移灶〈8),组2(转移灶≥8)。比较两组的总体生存率及无复发生存率,并通过多因素分析确定其不良预后因素。结果共有849人纳入研究, | Viganò L Capussotti L Magno P 王石 黄帆 | 2017 | 肝胆外科杂志2017，25，5： | 0 |
| 20 | 肝切除治疗八个或更多结肠癌肝脏转移灶显示文摘背景:对于具有大量肝转移灶的结肠癌病人,手术切除可能是有效的治疗方法,但其确切的益处尚不清楚。方法从两个具有大样本容量的肝脏外科中心收集1998至2012年间施行手术切除的结肠癌肝转移的病人数据,并根据其转移灶的数量进行分组:组1(转移灶〈8),组2(转移灶≥8)。 | Viganò LI Capussotti L Magno P Toso C Ferrero A De Rosa G Rubbia-Brandt L Mentha G Br J Surg 王石 耿小平 | 2017 | 肝胆外科杂志2017，25，3： | 0 |
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