Upregulation Of Renal GLUT2 And SGLT2 Is Involved In High-Fat Diet-Induced Gestational Diabetes In Mice

Abstract

Yong-Kuan Jiang,1,* Kai-Yue Xin,2,3,* Hong-Wei Ge,4 Fei-Juan Kong,5,6 Gang Zhao2,7 1Department of Anesthesiology, Ningbo No.6 Hospital, Ningbo, Zhejiang, People’s Republic of China; 2Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Cardiology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 4Department of Urology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 6Department of Endocrinology and Metabolism, Xuhui District Central Hospital of Shanghai, Shanghai, People’s Republic of China; 7Department of Cardiology, Kashgar Prefecture Second People’s Hospital, Kashi, Xinjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei-Juan KongDepartment of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Hongkou District, Shanghai 200080, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] ZhaoDepartment of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai 200032, People’s Republic of ChinaTel [phone] ext. 2745Fax [phone]Email [email protected]: Gestational diabetes mellitus (GDM) is a metabolic disorder during mid- to late-pregnancy characterized by hyperglycemia, insulin resistance and fetal mal-development. Glucose transporter type 2 (GLUT2) and sodium-coupled glucose cotransporters 2 (SGLT2) in the proximal tubules play a critical role in the reabsorption of glucose and have been linked to the occurrence of type 2 diabetes mellitus (T2DM). Our study was designed to investigate the role of GLUT2 and SGLT2 in the pathogenesis of GDM, which is considered a forerunner of T2DM, and investigate the related molecular mechanism.Methods: High-fat diet (HFD) was utilized to build a GDM mouse model that closely induces metabolic abnormalities similar to human GDM. Body weight, blood glucose and serum insulin were recorded in the experimental process. Glucose tolerance was determined by the use of an intraperitoneal glucose tolerance test (IPGTT). In addition, levels of GLUT2 and SGLT2 were evaluated to further explore the underlying mechanism of GDM.Results: HFD feeding induced abnormal glucose metabolism as manifested by increased levels of blood glucose and insulin and prominent glucose intolerance. Additionally, fetal mice from mother feed on HFD showed higher mean body weight. Furthermore, HFD feeding led to an increase in the number of positive cells of GLUT2 and SGLT2 in the renal proximal tubule and the expressions of renal GLUT2 and SGLT2 mRNA and proteins in mice. However, no obvious change was observed in renal morphology.Conclusion: Our study demonstrates a potential involvement of renal GLUT2 and SGLT2 in GDM pathology in an HFD-induced GDM mouse model, which further supports the role of renal GLUT2 and SGLT2 not only in T1DM and T2DM but also in GDM.Keywords: gestational diabetes mellitus, insulin resistance, renal threshold for glucose, GLUT2, SGLT2

Keywords

• Gestational diabetes mellitus
• Insulin resistance
• Renal threshold for glucose
• GLUT2
• SGLT2