Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice  

作　　者：Lakshini Y Herat Natalie C Ward Aaron L Magno Elizabeth P Rakoczy Marcio G Kiuchi Markus P Schlaich Vance B Matthews 

机构地区：[1]School of Biomedical Sciences,Dobney Hypertension Centre,Royal Perth Hospital Unit,University of Western Australia,Perth 6000,Australia [2]Faculty of Health and Medical Sciences,University of Western Australia,Crawley 6009,Australia [3]Faculty of Health Sciences,School of Public Health,Curtin University,Bentley 6102,Australia [4]Research Centre,Royal Perth Hospital,Perth 6000,Australia [5]Department of Molecular Ophthalmology,University of Western Australia,Crawley 6009,Australia [6]Dobney Hypertension Centre,School of Medicine,Royal Perth Hospital Unit,University of Western Australia,Perth 6000,Australia [7]Department of Cardiology and Department of Nephrology,Royal Perth Hospital,Perth 6000,Australia

出　　处：《World Journal of Gastroenterology》2020年第23期3225-3235,共11页世界胃肠病学杂志（英文版）

基　　金：Supported by the Royal Perth Hospital Medical Research Foundation,No.VMMRF2018。

摘　　要：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 mic

关 键 词：Sodium glucose co-transporter inhibitors Sodium glucose co-transporter 2 Diabetes Diabetic retinopathy MOUSE Gut microbiota Empagliflozin DAPAGLIFLOZIN SUCCINATE Akimba 

分 类 号：R587.1[医药卫生—内分泌]