Improved insulin sensitivity by GLUT12 overexpression in mice

Area of Science:

• Metabolic research
• Molecular biology
• Physiology

Background:

• The existence of insulin-sensitive glucose transporters (GLUTs) beyond GLUT4 is suggested by emerging evidence.
• Investigating novel GLUTs is crucial for understanding glucose homeostasis and developing metabolic therapies.

Purpose of the Study:

• To determine if glucose transporter 12 (GLUT12) functions as an insulin-sensitive GLUT.
• To characterize the metabolic effects of GLUT12 overexpression in vivo.

Main Methods:

• Generated transgenic (TG) mice overexpressing GLUT12 under a β-actin promoter.
• Assessed glucose metabolism using glucose and insulin tolerance tests and hyperinsulinemic-euglycemic clamps.
• Quantified basal and insulin-stimulated glucose clearance rates using [(3)H]-2-deoxy-D-glucose.

Main Results:

• GLUT12 overexpression (40-75%) in TG mice did not alter GLUT4 levels or body weight.
• TG mice exhibited improved oral glucose tolerance and enhanced insulin sensitivity.
• Insulin-stimulated glucose clearance rates were significantly increased in insulin-sensitive tissues of TG mice.

Conclusions:

• Increased GLUT12 expression enhances whole-body insulin sensitivity.
• This improvement is mediated by increased glucose clearance in insulin-responsive tissues under insulin stimulation.
• These findings identify GLUT12 as a novel, second insulin-sensitive glucose transporter.