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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 | Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study显示文摘 | Henry Krum Markus Schlaich Rob Whitbourn Paul A Sobotka Jerzy Sadowski Krzysztof Bartus Boguslaw Kapelak Anthony Walton Horst Sievert Suku Thambar William T Abraham Murray Esler | 2009 | The Lancet2009，，9671： | 2 |
| 3 | Ting Kau Bridge Hong Kong显示文摘 | Rudolf Bergerman Michael Schlaich | 1996 | Structural Engineering International1996，6，3： | 2 |
| 4 | Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study显示文摘 | Henry Krum Markus Schlaich Rob Whitbourn Paul A Sobotka Jerzy Sadowski Krzysztof Bartus Boguslaw Kapelak Anthony Walton Horst Sievert Suku Thambar William T Abraham Murray Esler | 2009 | The Lancet . 2009 (9671)2009，，9671： | 2 |
| 5 | Toward a consistent design of structural concrete 显示文摘 | Schlaich J Schafer K Jennewein M | 1987 | Journal of the Prestressed Concrete Institute1987，32，3： | 1 |
| 6 | Design and detailing of structural concrete using strut-and-tie models 显示文摘 | Schlaich J Schafer K | 1991 | The Structural Engineer1991，69，6： | 1 |
| 7 | Renalase plasma levels areassociated with systolic blood pressure in patients with resistanthypertension显示文摘 | Schlaich M Socra tous F Ekelis N | 2010 | J Hypertens2010，28，： | 1 |
| 8 | Effects of renal denervation on sympathetic activation,blood pressure,and glucose metabolism in patients with resistant hypertension显示文摘 | Schlaich MP Hering D Sobotka P | | 0，，： | 1 |
| 9 | Relation between QT interval variability and cardiac sympathetic activity'in hyper- tension显示文摘 | Baumert M Schlaich MP Nalivaiko E | 2011 | Am J Physiol Heart Circ Physiol2011，300，4： | 1 |
| 10 | Catheter-based renal sympathetic denervation for resistant hypertension:a multicentre safety and proof-of-principle cohort study显示文摘 | Krum H Schlaich M Whitbourn R | | 0，，9671： | 1 |
| 11 | Obesity-induced hyperten- sion and target organ damage current knowledge and future directions 显示文摘 | Schlaich MP Grassi G Lambert GW | 2009 | J Hypertens2009，27，2： | 1 |
| 12 | Renal denervation: a potential new treatment modality for polycystic ovary syndrome? 显示文摘 | Schlaich MP Straznicky N Grima M | 2011 | J Hypertens2011，29，5： | 1 |
| 13 | Renal sympatheticnerve ablation for uncontrolled hypertension显示文摘 | Schlaich MP Sohotka PA Krum H | | 0，，9： | 1 |
| 14 | Renin-angiotensin system and cardiovascular risk显示文摘 | SCHMIEDER R E HILGERS K F SCHLAICH M P | 2007 | Lancet2007，369，： | 1 |
| 15 | Catheter-based renal sympathetic denervation for resistant hypertension :a multicentre safety and proof-of-pnncple cohort study 显示文摘 | Krum H Schlaich M Whitboum R | 2009 | Lancet2009，373，： | 1 |
| 16 | Effect of renal sympathetic denervation on glucose metabolism in patients with resistant hypertension: A pilot study显示文摘 | Mahfoud F Schlaich M Kindermann I | 2011 | Circulation2011，123，18： | 1 |
| 17 | Renal sympathetic denervation for treatment of drug-resistant hypertension:one-year results from the symplicity HTN-2 randomized,controlled trial显示文摘 | Esler MD Krum H Schlaich M | 2012 | Circulation2012，126，25： | 1 |
| 18 | Catheter-based renal sympathetic denervation for resistant hypertension:a multicentre safety and proof-of-principle cohort study显示文摘 | Krum H Schlaich M Whitbourn R | | 0，，： | 1 |
| 19 | Catheter-based renal sympathetic denervation for resistant hypertension:a multicenter safety and proof-of-prlnciple cohort study显示文摘 | Krum H Schlaich M Whitbourn R | 2009 | Lancet2009，373，： | 1 |
| 20 | Recovery and neurological examination after remifentanil-desflurane or fentanyl-desflurane anaesthesia for carotid artery surgery显示文摘 | Wilhelm W Schlaich N Harrer J | 2001 | Br J Anaesth2001，86，： | 1 |
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