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

Abstract

Introduction

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

Acknowledgment

This work was supported by the Medical Research Project of Shanghai Xuhui District (No. SHXH201836), Special Study of Zhongshan Hospital of Fudan University (No. 201801), Natural Science Foundation of Xinjiang Uygur Autonomous Region (No. 2019D01C090), and Domestic Technical Cooperation Projects of Shanghai Science and Technology Commission (No. 19695840200).

Disclosure

The authors declare no conflicts of interest, financial or otherwise in this work.