Insulin resistance, hypertension and the insulin-responsive glucose transporter, GLUT-4

Campbell, Ian William (1997) Insulin resistance, hypertension and the insulin-responsive glucose transporter, GLUT-4. PhD thesis, University of Glasgow.

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Abstract

Insulin resistance is a disease state characterised by the reduced ability of insulin to exert its effects in peripheral tissues, skeletal muscle and adipose tissue. This condition has been associated with a number of other disease states including obesity and hypertension. The hypertensive Milan rat has previously been shown to be insulin resistant. Unlike any other hypertensive, insulin resistant model, the Milan rat has a normotensive, isogenic control which responds normally to insulin. As GLUT-4, the insulin-stimulated glucose transporter, had been implicated in insulin resistance I examined the levels of GLUT-4 present in the Milan rat. Results suggest that the insulin resistance experienced by this hypertensive strain may be due to a reduction in GLUT-4 within the intracellular membranes of skeletal muscle. This is due to the nature of insulin-stimulated glucose transport, which arises as a result of GLUT-4 translocatlng to the cell surface from an intracellular pool, and therefore increasing the rate of glucose uptake. Consequently, any reduction in intracellular GLUT-4may account for the insulin resistance observed. Further studies eXamined the stroke-prone spontaneously hypertensive rat, and the stroke-prone spontaneously hypertensive rat F2 generation. The F2 generation contains individuals that are extremely hypertensive and others which are normotensive. This was done to determine if the decrease in GLUT-4 observed in the hypertensive Milan rat correlated with increasing blood pressure. The results suggest that GLUT-4 levels in the stroke-prone spontaneously hypertensive rat are not altered by an increase in blood pressure. This result is in agreement with most studies on skeletal muscle GLUT-4, and highlights the complex nature of insulin resistance associated with hypertension. The concluding chapter discusses the effects of oestrogen, and derivatives, on insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Previous studies have shown that females taking steroid hormones, either by means of the contraceptive pill, of hormone replacement therapy, tend to suffer from insulin resistance. In 3T3-L1 adipocytes a 48 hour treatment with 30nM oestrogen significantly reduces insulin-stimulated glucose transport. This demonstrates that the cells have developed insulin resistance. However these cells do not have reduced GLUT-4 levels and the insulin resistance, induced by oestrogen, occurs by an as yet unknown mechanism.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Subjects: Q Science > QH Natural history > QH301 Biology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology > Molecular Cell and Systems Biology
Supervisor's Name: Gould, Professor Gwyn
Date of Award: 1997
Depositing User: Adam Swann
Unique ID: glathesis:1997-8472
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 04 Oct 2017 14:27
Last Modified: 04 Oct 2017 14:27
URI: http://theses.gla.ac.uk/id/eprint/8472

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