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

Collison, M., James, D., Graham, D., Holman, G., Connell, J., Dominiczak, A.F., Gould, G. and Salt, I. (2005) Reduced insulin-stimulated GLUT4 bioavailability in stroke-prone spontaneously hypertensive rats. Diabetologia, 48(3), pp. 539-546. (doi: 10.1007/s00125-005-1674-x)

Abstract

Aims/hypothesis: Insulin-stimulated glucose transport is impaired in a genetic model of hypertension, the stroke-prone spontaneously hypertensive rat (SHRSP), yet the molecular mechanisms that underlie this defect in the animals remain unclear. Methods: We examined the effects of insulin on the trafficking of the insulin-responsive glucose transporter GLUT4 to the plasma membrane in isolated adipocytes from SHRSP and normotensive control Wistar-Kyoto (WKY) rats. Results: Treatment of isolated adipocytes with insulin resulted in trafficking of GLUT4 to the plasma membrane. There was no significant difference in the magnitude of insulin-stimulated GLUT4 trafficking from intracellular membranes to the plasma membrane between strains. In contrast, we demonstrated that there is a significant reduction in GLUT4 accessible to the glucose photolabel Bio-LC-ATB-BGPA at the plasma membrane of SHRSP adipocytes compared with control rats. Conclusions/interpretation: We propose that a large proportion of GLUT4 translocated to the plasma membrane in response to insulin is not able to bind substrate and catalyse transport in the SHRSP. Therefore, there is a reduction in bioavailable GLUT4 in SHRSP animals that is likely to account, at least in part, for the reduced insulin-stimulated glucose uptake.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gould, Professor Gwyn and Salt, Dr Ian and Dominiczak, Professor Anna and Connell, Professor John
• Authors: Collison, M., James, D., Graham, D., Holman, G., Connell, J., Dominiczak, A.F., Gould, G., and Salt, I.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Diabetologia
• ISSN: 0012-186X