Normal β-Cell Glut2 Expression Is not Required for Regulating Glucose-Stimulated Insulin Secretion and Systemic Glucose Homeostasis in Mice

Abstract

Objective: Glucose transporter 2 (GLUT2) is expressed in the pancreatic β-cell, intestine, liver, and kidney in mice. Although GLUT2 is considered as a major regulator of insulin secretion, in vivo contribution of β-cell Glut2 to glucose-stimulated insulin secretion and systemic glucose homeostasis is undefined. Therefore, the main objective of this study is to determine the role of β-cell Glut2 in regulating insulin secretion and blood glucose levels in mice. Methods: We produced mice in which we can knock down Glut2 at a desired time specifically in β-cells (β-Glut2 KD) by crossing Glut2LoxP/LoxP mice with Ins1CreERT2 mouse strain and using the Cre-Lox recombination technique. We measured fasting blood glucose levels, glucose tolerance, and glucose-stimulated insulin secretion in the β-Glut2 KD mice. We used qRT-PCR and immunofluorescence to validate the deficiency of β-cell Glut2 in β-Glut2 KD mice. Results: We report that both male and female β-Glut2 KD mice have normal glucose-stimulated insulin secretion. Moreover, the β-Glut2 KD mice exhibit normal fasting blood glucose levels and glucose tolerance. The β-Glut2 KD mice have upregulated GLUT1 in islets. Conclusions: Our findings demonstrate that normal β-cell Glut2 expression is not essential for regulating glucose-stimulated insulin secretion and systemic glucose homeostasis in mice. Therefore, the currently assumed role of β-cell GLUT2 in regulating insulin secretion and blood glucose levels needs to be recalibrated. This will allow an opportunity to determine the contribution of other β-cell glucose transporters or factors whose normal expression may be necessary for mediating glucose stimulated insulin secretion.