Reduced insulin-stimulated GLUT4 bioavailability in stroke-prone spontaneously hypertensive rats

Area of Science:

• Physiology
• Metabolic Research
• Hypertension Studies

Background:

• Insulin-stimulated glucose transport is crucial for maintaining glucose homeostasis.
• Stroke-prone spontaneously hypertensive rats (SHRSP) exhibit impaired glucose transport.
• The molecular basis for this defect in SHRSP remains largely unknown.

Purpose of the Study:

• To investigate the molecular mechanisms of impaired insulin-stimulated glucose transport in SHRSP.
• To examine the trafficking and functionality of the glucose transporter GLUT4 in SHRSP adipocytes.

Main Methods:

• Isolated adipocytes from SHRSP and Wistar-Kyoto (WKY) rats were used.
• Insulin's effect on GLUT4 translocation to the plasma membrane was assessed.
• GLUT4 accessibility to a glucose photolabel (Bio-LC-ATB-BGPA) at the plasma membrane was measured.

Main Results:

• Insulin stimulated GLUT4 trafficking to the plasma membrane in both SHRSP and WKY rats.
• No significant difference was observed in the magnitude of GLUT4 translocation between the strains.
• SHRSP adipocytes showed a significant reduction in plasma membrane-accessible GLUT4 compared to WKY rats.

Conclusions:

• A substantial portion of translocated GLUT4 in SHRSP is functionally impaired, unable to bind substrate or catalyze transport.
• Reduced bioavailable GLUT4 at the plasma membrane likely contributes to impaired insulin-stimulated glucose uptake in SHRSP.
• This study elucidates a key molecular defect underlying glucose transport impairment in a genetic model of hypertension.