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


Reference:

Collison, M., James, D. J., Graham, D., Holman, G. D., Connell, J. M. C., Dominiczak, A. F., Gould, G. W. and Salt, I. P., 2005. Reduced insulin-stimulated GLUT4 bioavailability in stroke-prone spontaneously hypertensive rats. Diabetologia, 48 (3), pp. 539-546.

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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.

Details

Item Type Articles
CreatorsCollison, M., James, D. J., Graham, D., Holman, G. D., Connell, J. M. C., Dominiczak, A. F., Gould, G. W. and Salt, I. P.
DOI10.1007/s00125-005-1674-x
DepartmentsFaculty of Science > Biology & Biochemistry
RefereedYes
StatusPublished
ID Code3847
Additional InformationID number: ISI:000227741800017

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